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[(2.2)-298.5(Genomic)-302.7(characterization)-308.1(of)-300.3(HPV)]TJ /F8 1 Tf 9 0 0 9 318.8409 731.6786 Tm [(T)-9.6(h)0(e)-508.1(HPV)-513.3(v)-8.1(ira)-9.9(l)-505.9(par)-14.4(tic)-11(le)-8(s)-505.3(a)0(r)-11.6(e)-503.7(co)-10(mp)-9.7(ose)-11.3(d)-506.8(o)0(f)-506.6(a)-507.9(s)-7.7(ing)-13.4(le)-505.7(d)-9.1(oub)-10.7(le)-8(-)]TJ -1.5496 -1.3921 TD 0.0101 Tc [(stranded)-509.3(DNA)-512.3(m)3.2(olec)10.1(u)-11.4(l)1.8(e)10.1(,)-521.3(wi)10.1(t)-7.4(h)-510.9(a)10.1(p)-9.3(proximate)10.1(l)-10.5(y)-508.3(8)10.1(,000)-506.2(base)-512.5(p)1(airs)]TJ 0 -1.3858 TD 0 Tc [(\(bp\),)-450.8(and)-448.4(a)-451.2(protein)-448.2(capsid)-456.2(containing)-449.5(72)-453(pentameric)-454.5(capsomers)]TJ 0 -1.3921 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3402 0 TD (16)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-453.2(The)-448.4(genomes)-448.9(of)-449.9(all)-448.8(HPV)-444(types)-453.4(contain)-448.6(about)-449.6(eight)-451.9(open-)]TJ -1.2976 -1.3858 TD [(reading)-411.8(frames)-415.2(\(ORFs\))-415.6(that)-412.2(can)-413.9(be)-413.1(functionally)-418.2(divided)-416.1(into)-412.7(the)]TJ 0 -1.3921 TD [(early)-248.2(\(E\),)-247.4(the)-250.2(late)-245.4(\(L\),)-253.2(and)-246.9(the)-250.2(long)-247.8(control)-245.1(region)-251.5(\(LCR\))-246.8(\()]TJ 0.85098 0.19216 0.2 scn 22.9543 0 TD [(Figure)-252.5(1)]TJ 0.15294 0.15294 0.15294 scn 3.2693 0 TD (\).)Tj -26.2236 -1.3858 TD 0.0312 Tc [(S)7.9(p)3.2(eci)]TJ /F9 1 Tf 2.2173 0 TD 0 Tc ()Tj /F8 1 Tf 0.5606 0 TD 0.029 Tc [(cally,)-527.8(t)3.4(he)-525.1(E)-530.3(g)2(en)3.1(e)-525.1(e)-2.2(n)3.1(c)-2.2(odes)-526.7(t)3.4(h)-0.6(e)-525.1(e)-2.2(arly)-527.2(prote)4.1(i)-0.8(n)3.1(s)-526.7(\(E1)]TJ /F12 1 Tf 22.0284 0 TD 0 Tc ()Tj /F8 1 Tf 0.5354 0 TD 0.0301 Tc [(E7)5.2(\))]TJ -25.3417 -1.3921 TD 0.0109 Tc [(responsible)-511.7(f)-0.5(or)-513.3(vira)-5.6(l)-507.6(r)-3.1(eplicati)-6.3(on)-512.7(and)-508.5(o)0.7(ncogenesis.)-514.4(T)1.3(he)-511.7(L)-516.4(g)2.8(ene)]TJ 0 -1.3858 TD 0.0207 Tc [(encodes)-522.4(t)1.4(he)-520.8(structura)4.2(l)-523(proteins)-522.4(\(L1)]TJ /F12 1 Tf 15.6031 0 TD 0 Tc ()Tj /F8 1 Tf 0.5354 0 TD 0.0183 Tc [(L2)-6.6(\))-520.6(n)-1.3(e)-6.6(cess)-8.3(a)1.8(ry)-525.3(f)-5.7(o)1.8(r)-524.8(v)-2.4(ir)-8.3(io)-4.5(n)]TJ -16.1386 -1.3858 TD 0 Tc [(assembly.)-300.6(The)-303.6(non-coding)-307.5(region)-301.9(is)-302(thought)-307.9(to)-300.4(be)-299.7(the)-306.9(most)-302.3(highly)]TJ 0 -1.3921 TD [(variable)-204(part)-203.8(of)-198(the)-206.1(viral)-202.6(genome)-201.9(\()]TJ 0.85098 0.19216 0.2 scn 13.2598 0 TD (17)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-201.2(The)-202.8(structural)-211.4(capsid)-204.2(proteins)]TJ -14.2173 -1.3858 TD [(of)-393.2(HPVs)-401.2(are)-395.6(composed)-399.2(of)-399.6(two)-398.2(key)-394.5(proteins,)-401.6(major)-396(basic)-404.1(L1)-394.7(and)]TJ 0 -1.3921 TD [(min)-12.2(or)-509.2(ba)-7.9(sic)-515.9(L2)-10.5(,)-506.4(res)-15.1(pe)-8.9(cti)-11(ve)-7.9(ly)-507.7(en)-13.1(cod)-12.8(ed)-512.8(by)-509.7(L1)-508.1(an)-11(d)-506.8(L)0(2)-514.4(g)0(e)-7.9(nes)-14.4(.)-506.4(L)0(1)]TJ 0 -1.3858 TD [(ge)-7.9(n)-7(o)0(m)-10.8(e)0(s)-517.6(dis)-15(p)-9.1(lay)-518(d)-9.1(i)0(f)53.4(f)0(e)-11.1(r)-7.7(ent)-13.4(l)-8.3(y)-505.8(a)-10.2(m)-6.9(on)-11(gs)-9.5(t)-510.6(HPV)-519.6(t)-6.7(y)-8.1(pe)-8.9(s)-7.7(,)-506.4(w)-9.6(h)0(i)-9(l)-8.3(e)-510(t)0(h)-11.1(e)-510(L2)]TJ 0 -1.3921 TD [(genomic)-326.1(sequence)-331.7(is)-327.2(relatively)-332.3(conserved)-332.5(\()]TJ 0.85098 0.19216 0.2 scn 17.2284 0 TD (18)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-327.2(The)-328.8(HPV)-330.6(capsid)-330.2(is)]TJ -18.1858 -1.3858 TD [(made)-315.8(up)-314.3(of)-317.7(360)-314.2(copies)-314.5(of)-317.7(major)-314.1(\(L1\))-319.7(and)-316.2(72)-314.4(copies)-314.5(of)-317.7(minor)-313.5(\(L2\))]TJ 0 -1.3921 TD [(capsid)-210.5(proteins)-210.1(\()]TJ 0.85098 0.19216 0.2 scn 6.5512 0 TD (19)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-207.5(The)-215.4(L1)-205.7(protein)-215.1(is)-207.5(self-assembled)-217.6(into)-211.2(the)-206.1(virus-)]TJ -7.5087 -1.3858 TD [(like)-424.4(particles)-431.6(\(VLP\),)-430.4(while)-423.5(the)-426.6(L2)-426.2(protein,)-431.7(as)-427.3(a)-426(minor)-426.9(structural)]TJ 0 -1.3921 TD [(molecule,)-328(is)-333.5(unable)-334.4(to)-331.9(form)-332.2(VLPs.)-330.3(Although)-334.4(the)-325.8(L2)-331.7(protein)-334.8(is)-333.5(not)]TJ 0 -1.3858 TD [(responsible)-311.3(for)-312.7(binding)-308.9(to)-306.7(and)-316.2(entering)-311.4(cells)-307.1(during)-316.5(the)-306.9(process)-312.7(of)]TJ 0 -1.3921 TD [(infection,)-343.2(it)-345.1(plays)-352.1(a)-344.1(key)-344.1(role)-347.2(in)-345.5(enhancing)-344(L1)-350.6(assembly)-342.3(into)-349.7(VLPs)]TJ 0 -1.3858 TD [(and)-297.3(viral)-303.4(genome)-302.6(encapsidation)-306.4(\()]TJ 0.85098 0.19216 0.2 scn 13.4803 0 TD (20)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-302(Once)-300.6(entering)-305.1(host)-306.1(cells,)-303.3(the)]TJ -14.4378 -1.3921 TD [(viral)-309.7(E6)-307(and)-309.9(E7)-307(oncoproteins)-319.3(are)-307.4(responsible)-311.3(for)-312.7(viral)-309.7(oncogenesis)]TJ 0 -1.3858 TD [(by)-327(af)60.3(fecting)-339.6(the)-332.1(function)-339.2(of)-330.3(tumor)-336.6(suppressors)-341.5(p53)-329.9(and)-335.1(pRB)-336.5(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (21)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD [(HPV)-292.8(types)-295.9(that)-292.6(cause)-291.1(genital)-296.6(warts)-293.8(are)-294.8(called)-293.7(low-risk,)-297.2(while)-291.2(those)]TJ 0 -1.3858 TD [(types)-220.3(that)-223.3(cause)-228.1(cervical)-220.8(cancer)-225.7(are)-225.5(considered)-224.7(high-risk)-225.2(\()]TJ 0.85098 0.19216 0.2 scn 22.6772 0 TD (22)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-226.4(High-)]TJ ET 0.63529 0.63529 0.63529 scn 304.894 397.984 m 545.953 397.984 l 545.726 397.757 l 305.121 397.757 l f* 545.953 397.984 m 545.953 127.332 l 545.726 127.616 l 545.726 397.757 l f* 545.953 127.332 m 304.894 127.332 l 305.121 127.616 l 545.726 127.616 l f* 304.894 127.332 m 304.894 397.984 l 305.121 397.757 l 305.121 127.616 l f* q 319.124 385.228 m 531.666 385.228 l 531.666 197.575 l 319.124 197.575 l W n q 212.541672 0 0 187.653473 319.124329 197.574829 cm /Im2 Do Q Q BT /F5 1 Tf 5.5001 0 0 5.5001 316.1196 185.1024 Tm 0.49804 0.49804 0.49412 scn [(FIGURE)-305.5(1)]TJ /F3 1 Tf 6.9999 0 0 6.9999 316.1196 176.0882 Tm [(HPV)-302.7(genome)-303.1(organization.)-301.7(The)-298.7(genome)-303.1(of)-305.1(HPVs,)-299(about)-300.9(8000)-302(base)]TJ 0 -1.2878 TD [(pairs)-300.6(in)-297.6(length,)-308.8(is)-297.8(consists)-301(of)-305.1(approximately)-307.2(eight)-298.5(open)-300.3(reading)]TJ 0 -1.2797 TD [(frames)-298.3(\(ORFs\),)-303.9(which)-302.1(can)-301.7(be)-298.6(functionally)-309.2(categorized)-305.2(into)-298.2(three)]TJ 0 -1.2878 TD 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[(and)-366.6(HPV-18,)-362.8(responsible)-367.9(for)-363.1(nearly)-368.6(70%)-364.4(of)-361.7(cervical)-365.6(cancers)-365.7(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (24)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD (Cervarix)Tj /F13 1 Tf 7.4999 0 0 7.4999 80.4472 513.4109 Tm ()Tj /F8 1 Tf 9 0 0 9 88.4409 509.3857 Tm [(is)-264.2(formulated)-268.3(in)-263.6(a)-262.2(proprietary)-263.5(AS04)-268.1(adjuvant)-264.1(containing)]TJ -4.315 -1.3858 TD [(aluminum)-295.2(hydroxide)-290.5(combined)-293.2(with)-296.1(a)-287.4(Toll-like)-295.7(receptor)-292.5(4)-289.5(\(TLR4\))]TJ 0 -1.3921 TD [(ligand,)-314.4(3-O-desacyl-4)]TJ /F12 1 Tf 8.6236 0 TD ()Tj /F8 1 Tf 0.2142 0 TD [(-monophosphoryl)-314(lipid)-312.8(A)-308.3(\(MPL\))-315.5(\()]TJ 0.85098 0.19216 0.2 scn 13.9969 0 TD (25)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (26)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-314.6(It)]TJ -25.2787 -1.3858 TD [(is)-402.8(indicated)-409.9(for)-400.9(use)-407.1(in)-402.1(females)-403(aged)-405.2(10)-402.6(through)-409.7(25)-402.6(years)-405.1(for)-400.9(the)]TJ 28.3654 31.8866 TD [(prevention)-469.4(of)-462.5(persistent)-472.2(infection,)-469.1(premalignant)-469.8(cervical)-466.4(lesions,)]TJ 0 -1.3858 TD [(and)-297.3(cervical)-302.7(cancer)-307.6(caused)-300.2(by)-301.8(HPVs)-306.7(in)-295.1(the)-306.9(US.)]TJ 1.5496 -1.3921 TD [(Ga)17.4(rd)21(as)19.9(i)14.3(l)]TJ /F13 1 Tf 7.4999 0 0 7.4999 348.1511 737.9148 Tm ()Tj /F8 1 Tf 9 0 0 9 353.707 733.8896 Tm [(,)-260.7(a)-255.9(q)12.4(u)0(a)18.4(d)0(r)21(i)0(v)18.8(a)15(le)17.2(nt)-246.8(HP)18.1(V)-260.5(v)0(a)25.7(c)0(c)19.4(i)0(n)19.9(e)12.9(,)-260.7(i)0(s)-251.6(t)0(h)20.4(e)]TJ /F9 1 Tf 14.2992 0 TD ()Tj /F8 1 Tf 0.5165 0 TD [(rs)16.2(t)-258.6(c)12.9(om)20.7(me)18.6(rc)24.1(ia)23(ll)21.3(y)]TJ -20.2394 -1.3858 TD [(a)15(v)0(a)19.4(i)14.3(la)19.3(bl)19.3(e)-390.3(H)0(P)18.1(V)-392.8(va)19.4(c)12.8(c)0(i)20.9(n)0(e)-384.7(a)0(p)18.4(p)0(r)21(o)15(ve)17.3(d)-393.4(i)0(n)-383.3(2)12.9(00)19.4(6)-396.6(f)13.8(or)-383.2(pe)16.3(o)15(p)0(l)20.4(e)-396.6(9)-390.3(t)0(h)20.4(r)0(o)19.9(u)0(g)20.5(h)-395(2)12.9(6)]TJ 0 -1.3921 TD [(y)17.1(e)0(a)15.2(r)0(s)-286.2(o)15(f)-301.1(a)0(g)19.4(e)-295.8(fo)22.5(r)-297.4(t)0(h)20.4(e)-302.1(pr)21(e)12.8(v)0(e)23.6(n)0(t)17.8(i)14.3(on)-288.1(of)-292.5(d)16.1(i)0(s)19.3(e)12.9(as)19.9(es)-290.9(c)12.8(a)0(u)18.4(s)0(e)24.1(d)-298.9(by)-289.2(HP)24.4(V)-304.6(i)14.3(nf)19.4(e)12.8(c)0(t)18.8(i)14.3(on)]TJ 0 -1.3858 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3276 0 TD (27)Tj 0.15294 0.15294 0.15294 scn 0.9386 0 TD [(\).)-396.5(As)17.9(i)14.3(d)0(e)-399.4(f)0(r)18.8(o)15(m)-410(H)0(P)18.1(V)0(-)24.2(1)12.9(6)-409.2(a)0(n)20.5(d)-412.3(1)12.9(8)12.9(,)-411.9(G)15.1(a)0(r)19.9(d)0(a)18.4(s)0(i)25.6(l)]TJ /F13 1 Tf 7.4999 0 0 7.4999 463.0109 700.3842 Tm ()Tj /F8 1 Tf 9 0 0 9 472.3085 696.4156 Tm [(al)19.3(so)-395.8(pr)21(ot)20.9(e)12.8(c)0(t)18.8(s)-410.8(a)15(g)0(a)19.4(i)0(n)19.9(s)0(t)]TJ -18.6016 -1.3921 TD [(H)16.7(P)0(V)18.1(-)13.8(6)-232.8(a)15(nd)-217.7(-1)20.4(1)-226.5(i)14.3(nf)19.4(ec)19.4(ti)20.3(o)15(n)0(s)16.8(,)-222.9(wh)17.5(i)14.3(c)0(h)-218.3(c)12.8(au)18.4(se)-215.3(ap)18.4(pr)21(o)15(x)0(i)16.2(m)0(a)20.7(t)0(e)25.1(l)0(y)-218(9)12.9(0)12.9(%)-226.4(of)-216.9(ge)17.3(ni)26.2(ta)20.9(l)]TJ 0 -1.3858 TD 0.037 Tc [(wart)5.1(s.)-551.3(Gardasil)]TJ /F13 1 Tf 7.4999 0 0 7.4999 365.7826 675.3826 Tm 0 Tc ()Tj /F8 1 Tf 9 0 0 9 376.6676 671.4141 Tm 0.0359 Tc [(is)-545(a)-5.8(d)1.6(sorbed)-546.5(on)-550.7(an)-550.7(amorpho)-5.8(u)1.6(s)-551.3(a)0.5(lu)-4.7(minu)-4.7(m)]TJ -7.9748 -1.3921 TD 0 Tc [(h)14.5(y)0(d)20.5(r)0(o)19.9(x)14.5(yp)20.5(ho)23.1(sp)21(ha)16.8(te)-277.3(su)21(lf)24.5(at)20.9(e)-289.5(a)0(d)18.4(j)0(u)20.4(v)0(a)25.7(n)0(t)-278.3(\()]TJ 0.85098 0.19216 0.2 scn 14.3622 0 TD (28)Tj 0.15294 0.15294 0.15294 scn 0.9386 0 TD (\).)Tj -13.7512 -1.3858 TD 0.0104 Tc [(Gardasil)-508.1(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 358.6393 650.381 Tm 0 Tc ()Tj /F8 1 Tf 9 0 0 9 364.3653 646.4125 Tm 0.0103 Tc [(,)-508.7(l)2(ic)10.3(e)-8.1(n)-3(sed)-509.1(b)0.1(y)-508.1(t)3.6(he)-512.3(FDA)-512.1(i)10.3(n)-517.8(2)10.3(0)-8.1(1)-2(4)10.3(,)-514.7(of)61.9(fe)10.3(r)-9.7(s)-507.6(broader)]TJ -6.6079 -1.3921 TD 0 Tc [(protection)-464.8(by)-459.3(covering)]TJ /F9 1 Tf 9.8835 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(ve)-461.4(additional)-470.6(HPV)-462.9(types)-459.7(\(HPV-31,)-467(33,)]TJ -10.4126 -1.3858 TD [(45,)-247.6(53,)-253.9(and)-253.2(58\))-254.9(that)-254.8(might)-251.2(account)-256.9(for)-256(about)-254.4(20%)-251(of)-254.7(cervical)-252.3(cancer)]TJ 0 -1.3921 TD [(cases)-321.1(\()]TJ 0.85098 0.19216 0.2 scn 2.6646 0 TD (29)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-320.9(Gardasil)-326.1(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 382.7338 612.907 Tm ()Tj /F8 1 Tf 9 0 0 9 391.2944 608.8818 Tm [(is)-320.9(indicated)-328(for)-325.3(females)-327.4(aged)-323.3(9)-321(through)-327.8(45)]TJ -9.6 -1.3858 TD [(years)-323.2(for)-325.3(the)-319.5(prevention)-330.8(of)-317.7(HPV-associated)-332.2(diseases.)-326(Additionally,)]TJ 0 -1.3921 TD [(Gardasil)-288.3(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 341.8582 587.9054 Tm ()Tj /F8 1 Tf 9 0 0 9 350.0786 583.8802 Tm [(is)-289.4(indicated)-296.5(in)-288.8(males)-291.1(9)-289.5(through)-290(45)-289.2(years)-291.7(of)-292.5(age)-289(for)-293.8(the)]TJ -5.0205 -1.3858 TD 0.0297 Tc [(prevention)-525.4(of)-529.7(anal,)-527.1(o)0.6(ropharyn)]TJ 13.5685 0 TD 0.0263 Tc [(ge)-4.9(al,)-536.8(h)-3.3(ea)-9.1(d)-530.9(n)-5.9(ec)-4.9(k)-536.7(c)1.4(a)-9.1(n)0.4(c)-5(e)-4.9(rs)-6.6(,)-530.5(a)-2.8(n)-5.9(a)-2.8(l)]TJ -13.5685 -1.3921 TD 0 Tc [(precancerous,)-353.6(dysplastic)-354.6(lesions,)-356.3(and)-347.7(genital)-353.3(warts)-350.5(caused)-356.9(by)-345.9(HR-)]TJ 0 -1.3858 TD [(HPVs)-319.3(\()]TJ 0.85098 0.19216 0.2 scn 3.0488 0 TD (30)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-320.9(Gardasil)-326.1(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 386.192 550.3747 Tm ()Tj /F8 1 Tf 9 0 0 9 394.696 546.4062 Tm [(is)-320.9(formulated)-325(with)-327.6(amorphous)-321.2(aluminum)]TJ -9.978 -1.3921 TD [(hydroxyphosphate)-302.8(sulfate)-305(\(AAHS\))-302.5(as)-301.4(an)-300.7(adjuvant)-301.9(\()]TJ 0.85098 0.19216 0.2 scn 20.6929 0 TD (31)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -20.1008 -1.3858 TD [(Recently,)-387.9(two)-379.3(more)-383.6(bivalent)-382.4(HPV)-381(vaccines)-389.6(\(HPV-16)-382.7(and)-379.2(18\))]TJ -1.5496 -1.3921 TD [(have)-230.4(been)-237.2(approved)-239.8(in)-238.4(China)-233.2(for)-237.1(protection)-238(against)-237.2(HPV)-236.1(infection-)]TJ 0 -1.3858 TD [(induced)-246.3(precancerous)-250.4(lesions)-253(or)-244.7(high-grade)-244.2(genital)-252.5(lesions)-246.7(\()]TJ 0.85098 0.19216 0.2 scn 23.7921 0 TD (32)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9638 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (34)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD 0.0124 Tc [(Clinical)-512.4(data)-508.1(revealed)-507(that)-510.8(the)-510.2(2)0.1(-)-5.3(v)4.3(alent)-510.8(H)-2.4(PV)-512.7(vaccine)-510.2(showed)]TJ 0 -1.3858 TD 0 Tc [(favorable)-422.6(immunogenicity,)-425.9(safety,)-424.2(and)-423.3(a)-426(positive)-422.3(seroconvertsion)]TJ ET 0.49804 0.49804 0.49804 scn 49.833 401.726 496.006 27.666 re f 0.63529 0.63529 0.63529 scn 49.606 429.392 496.346 0.22678 re f 545.726 91.956 0.22681 337.436 re f 49.606 91.956 0.22676 337.436 re f 132.831 401.726 m 49.833 401.726 l 49.833 401.953 l 132.831 401.953 l 132.831 401.726 l f* 132.831 401.726 0.28346 27.666 re f 133.115 401.726 82.715 0.22678 re f 215.83 401.726 0.28345 27.666 re f 216.113 401.726 82.772 0.22678 re f 298.885 401.726 0.22678 27.666 re f 299.112 401.726 82.772 0.22678 re f 381.883 401.726 0.22678 27.666 re f 382.11 401.726 81.751 0.22678 re f 463.861 401.726 0.22678 27.666 re f 464.088 401.726 81.751 0.22678 re f 132.831 385.115 m 49.833 385.115 l 49.833 385.342 l 132.831 385.342 l 132.831 385.115 l f* 132.831 385.115 0.28346 16.611 re f 133.115 385.115 82.715 0.22678 re f 215.83 385.115 0.28345 16.611 re f 216.113 385.115 82.772 0.22678 re f 298.885 385.115 0.22678 16.611 re f 299.112 385.115 82.772 0.22678 re f 381.883 385.115 0.22678 16.611 re f 382.11 385.115 81.751 0.22678 re f 463.861 385.115 0.22678 16.611 re f 464.088 385.115 81.751 0.22678 re f 132.831 359.036 m 49.833 359.036 l 49.833 359.263 l 132.831 359.263 l 132.831 359.036 l f* 132.831 359.036 0.28346 26.079 re f 133.115 359.036 82.715 0.22678 re f 215.83 359.036 0.28345 26.079 re f 216.113 359.036 82.772 0.22678 re f 298.885 359.036 0.22678 26.079 re f 299.112 359.036 82.772 0.22678 re f 381.883 359.036 0.22678 26.079 re f 382.11 359.036 81.751 0.22678 re f 463.861 359.036 0.22678 26.079 re f 464.088 359.036 81.751 0.22678 re f 132.831 304.384 m 49.833 304.384 l 49.833 304.668 l 132.831 304.668 l 132.831 304.384 l f* 132.831 304.384 0.28346 54.652 re f 133.115 304.384 82.715 0.28345 re f 215.83 304.384 0.28345 54.652 re f 216.113 304.384 82.772 0.28345 re f 298.885 304.384 0.22678 54.652 re f 299.112 304.384 82.772 0.28345 re f 381.883 304.384 0.22678 54.652 re f 382.11 304.384 81.751 0.28345 re f 463.861 304.384 0.22678 54.652 re f 464.088 304.384 81.751 0.28345 re f 132.831 278.305 m 49.833 278.305 l 49.833 278.532 l 132.831 278.532 l 132.831 278.305 l f* 132.831 278.305 0.28346 26.079 re f 133.115 278.305 82.715 0.22678 re f 215.83 278.305 0.28345 26.079 re f 216.113 278.305 82.772 0.22678 re f 298.885 278.305 0.22678 26.079 re f 299.112 278.305 82.772 0.22678 re f 381.883 278.305 0.22678 26.079 re f 382.11 278.305 81.751 0.22678 re f 463.861 278.305 0.22678 26.079 re f 464.088 278.305 81.751 0.22678 re f 132.831 261.694 m 49.833 261.694 l 49.833 261.978 l 132.831 261.978 l 132.831 261.694 l f* 132.831 261.694 0.28346 16.611 re f 133.115 261.694 82.715 0.28348 re f 215.83 261.694 0.28345 16.611 re f 216.113 261.694 82.772 0.28348 re f 298.885 261.694 0.22678 16.611 re f 299.112 261.694 82.772 0.28348 re f 381.883 261.694 0.22678 16.611 re f 382.11 261.694 81.751 0.28348 re f 463.861 261.694 0.22678 16.611 re f 464.088 261.694 81.751 0.28348 re f 132.831 197.631 m 49.833 197.631 l 49.833 197.858 l 132.831 197.858 l 132.831 197.631 l f* 132.831 197.631 0.28346 64.063 re f 133.115 197.631 82.715 0.22676 re f 215.83 197.631 0.28345 64.063 re f 216.113 197.631 82.772 0.22676 re f 298.885 197.631 0.22678 64.063 re f 299.112 197.631 82.772 0.22676 re f 381.883 197.631 0.22678 64.063 re f 382.11 197.631 81.751 0.22676 re f 463.861 197.631 0.22678 64.063 re f 464.088 197.631 81.751 0.22676 re f 132.831 181.02 m 49.833 181.02 l 49.833 181.247 l 132.831 181.247 l 132.831 181.02 l f* 132.831 181.02 0.28346 16.611 re f 133.115 181.02 82.715 0.22676 re f 215.83 181.02 0.28345 16.611 re f 216.113 181.02 82.772 0.22676 re f 298.885 181.02 0.22678 16.611 re f 299.112 181.02 82.772 0.22676 re f 381.883 181.02 0.22678 16.611 re f 382.11 181.02 81.751 0.22676 re f 463.861 181.02 0.22678 16.611 re f 464.088 181.02 81.751 0.22676 re f 132.831 164.409 m 49.833 164.409 l 49.833 164.636 l 132.831 164.636 l 132.831 164.409 l f* 132.831 164.409 0.28346 16.611 re f 133.115 164.409 82.715 0.22675 re f 215.83 164.409 0.28345 16.611 re f 216.113 164.409 82.772 0.22675 re f 298.885 164.409 0.22678 16.611 re f 299.112 164.409 82.772 0.22675 re f 381.883 164.409 0.22678 16.611 re f 382.11 164.409 81.751 0.22675 re f 463.861 164.409 0.22678 16.611 re f 464.088 164.409 81.751 0.22675 re f 132.831 128.806 m 49.833 128.806 l 49.833 129.033 l 132.831 129.033 l 132.831 128.806 l f* 132.831 128.806 0.28346 35.603 re f 133.115 128.806 82.715 0.22675 re f 215.83 128.806 0.28345 35.603 re f 216.113 128.806 82.772 0.22675 re f 298.885 128.806 0.22678 35.603 re f 299.112 128.806 82.772 0.22675 re f 381.883 128.806 0.22678 35.603 re f 382.11 128.806 81.751 0.22675 re f 463.861 128.806 0.22678 35.603 re f 464.088 128.806 81.751 0.22675 re f 132.831 102.728 m 49.833 102.728 l 49.833 102.954 l 132.831 102.954 l 132.831 102.728 l f* 132.831 102.728 0.28346 26.079 re f 133.115 102.728 82.715 0.22678 re f 215.83 102.728 0.28345 26.079 re f 216.113 102.728 82.772 0.22678 re f 298.885 102.728 0.22678 26.079 re f 299.112 102.728 82.772 0.22678 re f 381.883 102.728 0.22678 26.079 re f 382.11 102.728 81.751 0.22678 re f 463.861 102.728 0.22678 26.079 re f 464.088 102.728 81.751 0.22678 re f 49.833 102.217 496.006 0.51022 re f 1 1 1 scn 540.85 91.956 4.989 10.261 re f 540.85 91.956 15.024 10.261 re f 49.833 91.956 5.0457 10.261 re f 39.855 91.956 15.024 10.261 re f 39.855 101.48 516.019 0.73703 re f BT /F5 1 Tf 6.9999 0 0 6.9999 49.6063 439.6534 Tm 0.49804 0.49804 0.49412 scn [(TABLE)-306.1(1)-794(Summary)-301.7(of)-303.6(marketed)-300.2(prophylactic)-308.8(HPV)-301.2(vaccines.)]TJ /F1 1 Tf 9 0 0 9 75.1748 417.5432 Tm 1 1 1 scn (Valency)Tj -1.285 -1.1087 TD [(\(Brand)-303.8(name\))]TJ 10.7969 1.1087 TD (2vHPV)Tj -0.9323 -1.1087 TD (\(Cervarix)Tj 6.0001 0 0 6.0001 189.0708 410.0598 Tm ()Tj 9 0 0 9 193.9464 407.5653 Tm (\))Tj 5.5181 1.1087 TD (4vHPV)Tj -0.8756 -1.1087 TD (\(Gardasil)Tj 6.0001 0 0 6.0001 271.729 410.0598 Tm ()Tj 9 0 0 9 276.6047 407.5653 Tm (\))Tj 5.5622 1.1087 TD (9vHPV)Tj -1.3291 -1.1087 TD [(\(Gardasil)-307.3(9)]TJ 6.0001 0 0 6.0001 358.7527 410.0598 Tm ()Tj 9 0 0 9 363.6282 407.5653 Tm (\))Tj 5.0709 1.1087 TD (2vHPV)Tj -0.8 -1.1087 TD (\(Cecolin)Tj 6.0001 0 0 6.0001 436.3652 410.0598 Tm ()Tj 9 0 0 9 441.2408 407.5653 Tm (\))Tj 5.5622 1.1087 TD (2vHPV)Tj -1.3354 -1.1087 TD (\(WalrinVax)Tj 6.0001 0 0 6.0001 523.162 410.0598 Tm ()Tj 9 0 0 9 528.0376 407.5653 Tm (\))Tj /F8 1 Tf 6.9999 0 0 6.9999 78.2929 391.181 Tm 0.15294 0.15294 0.15294 scn [(Approval)-9044.5(2009)-9941.2(2006)-9941.2(2014)-9876.4(2019)-9795.4(2022)]TJ -0.8828 -3.0453 TD [(Manufacturer)-4946.9(GlaxoSmithKline)-307(plc)-4143.2(Merck)-305.3(&)-304.4(Co.,)-295.1(Inc)-4792.5(Merck)-305.3(&)-304.4(Co.,)-295.1(Inc)]TJ 46.7806 0.6803 TD [(Xiamen)-298.8(Innovax)]TJ 1.6117 -1.3607 TD [(Co.,)-303.2(Ltd.)]TJ 10.1644 0.6803 TD [(Walvax)-302.7(Co.,)-303.2(Ltd)]TJ -59.2128 -5.0863 TD [(Vaccine)-307.8(antigens)]TJ 0.9557 -1.3607 TD [(\(L1)-299.2(protein\))]TJ 11.0229 1.3607 TD [(HPV-16)-297.5(\(20)]TJ /F14 1 Tf 5.232 0 TD (m)Tj /F8 1 Tf 0.575 0 TD (g\))Tj -5.8071 -1.3607 TD [(HPV-18)-297.5(\(20)]TJ /F14 1 Tf 5.232 0 TD (m)Tj /F8 1 Tf 0.575 0 TD (g\))Tj 4.6489 1.3607 TD [(HPV-6,18)-305.1(\(20)]TJ /F14 1 Tf 5.9286 0 TD (m)Tj /F8 1 Tf 0.575 0 TD [(g)-303.3(each\))]TJ -6.7466 -1.3607 TD [(HPV-11,16)-304(\(40)]TJ /F14 1 Tf 6.4145 0 TD (m)Tj /F8 1 Tf 0.575 0 TD [(g)-295.2(each\))]TJ 6.7466 3.3935 TD [(HPV-6)-306.7(\(30)]TJ /F14 1 Tf 4.7542 0 TD (m)Tj /F8 1 Tf 0.575 0 TD (g\))Tj -5.5641 -1.3526 TD [(HPV-16)-297.5(\(60)]TJ /F14 1 Tf 5.232 0 TD (m)Tj /F8 1 Tf 0.575 0 TD 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/F12 1 Tf 0.486 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (45)Tj 7.9695 0.6803 TD [(Females)-300.1(aged)-307.2(9)]TJ /F12 1 Tf 6.131 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(45)-4298.4(Female)-299.6(aged)-299.1(9)]TJ /F12 1 Tf 11.0229 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (30)Tj /F11 1 Tf -1.636 -2.9805 TD (\(Continued\))Tj /F1 1 Tf 0.49804 0.49804 0.49412 scn -66.0808 101.1825 TD [(Wang)-305.1(et)-300.8(al.)]TJ 57.1394 0 TD (10.3389/fimmu.2024.1362770)Tj -57.1394 -109.3302 TD [(Frontiers)-304.6(in)]TJ 0.85098 0.19216 0.2 scn 5.5074 0 TD (Immunology)Tj 58.8564 0 TD (frontiersin.org)Tj 0.15294 0.15294 0.15294 scn -29.5051 0 TD (03)Tj ET endstream endobj 49 0 obj<> endobj 50 0 obj<> endobj 51 0 obj<> endobj 52 0 obj<> endobj 53 0 obj<> endobj 54 0 obj<> endobj 55 0 obj<> endobj 56 0 obj<> endobj 57 0 obj<> endobj 58 0 obj<> endobj 59 0 obj<> endobj 60 0 obj<> endobj 61 0 obj<> endobj 62 0 obj<> endobj 63 0 obj<> endobj 64 0 obj<> endobj 65 0 obj<> endobj 66 0 obj<> endobj 67 0 obj<> endobj 68 0 obj<> endobj 69 0 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Tc [(adjuvants)-526.9(a)-0.3(nd)-528.4(antigen)-520(e)-2.4(xpress)]TJ 13.3669 0 TD 0.0184 Tc [(io)-4.4(n)-530.4(s)-1.9(y)-8.6(s)-1.9(t)-7.2(e)-6.5(ms)-8.2(.)-525.8(A)-529.2(co)-4.4(m)-7.4(p)-3.3(r)-8.2(e)-0.2(h)-4.9(e)-6.5(n)-7.5(s)-1.9(i)-5.1(v)-2.3(e)]TJ -13.3669 -1.3858 TD 0 Tc [(comparison)-306.4(of)-298.8(marketed)-307(HPV)-299.1(vaccines)-307.7(is)-295.7(shown)-303.5(in)]TJ 0.85098 0.19216 0.2 scn 21.0457 0 TD [(Table)-302.7(1)]TJ 0.15294 0.15294 0.15294 scn 2.9984 0 TD (.)Tj -22.4882 -1.3921 TD [(The)-259.5(immunogenicity)-259.7(and)-259.5(ef)]TJ /F9 1 Tf 11.0362 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-263.5(of)]TJ /F9 1 Tf 2.9732 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(ve)-259.9(licensed)-256.3(HPV)-261.3(vaccines)]TJ -16.6236 -1.3858 TD [(have)-280.8(been)-287.6(summarized)-288.4(elsewhere)-282.2(\()]TJ 0.85098 0.19216 0.2 scn 13.9717 0 TD (33)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5039 0 TD (38)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.4976 0 TD (39)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-283.1(Brie)]TJ /F9 1 Tf 2.4693 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(y,)-281.5(all)-285(marketed)]TJ -20.8504 -1.3921 TD 0.0253 Tc [(HPV)-524.9(v)4.6(accines)-524.1(e)0.4(licit)-529.4(p)3.6(otent)-523.1(h)-4.3(umoral)-524.7(im)5.8(mune)-522.5(responses)-524.1(a)-3.8(nd)]TJ 0 -1.3858 TD 0 Tc [(exhibited)-314.4(long-lasting)-305.4(protective)-316.8(ef)]TJ /F9 1 Tf 13.9213 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-313.9(after)-306.5(vaccination)-313.8(\()]TJ 0.85098 0.19216 0.2 scn 9.3858 0 TD (34)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5228 0 TD (40)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9575 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn -26.274 -1.3921 TD (43)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-396.5(Serum)-393.2(antibody)-393.8(responses)-396.6(are)-395.6(the)-395.1(major)-389.7(indicators)-395(used)-397.3(for)]TJ -0.9575 -1.3858 TD [(evalsuating)-494.2(immunogenicity)-492.8(evoked)-489.2(by)-490.8(HPV)-488.1(vaccines)-490.4(in)-490.3(clinical)]TJ 0 -1.3921 TD [(trials,)-286.9(and)-284.7(comparison)-287.5(of)-286.2(vaccine-induced)-293.2(antibody)-286.7(levels)-283.8(or)-282.4(B-cell)]TJ 0 -1.3858 TD [(response)-11(s)-499(between)-505.2(HPV)-507(vaccines)-503(have)-507.6(been)-501.8(discussed)-514.2(\()]TJ 0.85098 0.19216 0.2 scn 23.7921 0 TD (44)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9638 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (46)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD 0.0156 Tc [(Nevert)-3.7(heless)-4.7(,)-516(d)0.2(e)]TJ /F9 1 Tf 6.9543 0 TD 0 Tc ()Tj /F8 1 Tf 0.548 0 TD 0.0171 Tc [(n)3.8(i)-0.1(tive)-511.8(correlat)4.1(ion)-519.1(b)6.9(etwe)4.8(en)-519.1(h)6.4(u)-4.6(m)3.9(o)0.6(ral)-520.3(i)6.2(mmun)3.8(e)]TJ -7.5024 -1.3858 TD 0 Tc [(responses)-333.6(and)-328.8(ef)]TJ /F9 1 Tf 6.652 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(cacy)-326.5(of)-324(HPV)-330.6(vaccines)-332.9(has)-324.7(not)-332.6(yet)-323.2(been)-331.7(reported)]TJ -7.1874 -1.3921 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3465 0 TD (47)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-352.4(Prophylactic)-363.5(HPV)-355.8(vaccines)-358.1(based)-358.3(on)-357.4(L1-VLPs)-356(trigger)-357.5(T-cell)]TJ -1.3039 -1.3858 TD [(responses,)-329.8(which)-318.8(showed)-324.3(no)-319.6(correlation)-324(with)-321.3(protection,)-328.7(probably)]TJ 0 -1.3921 TD [(due)-200.7(to)-199.6(the)-206.1(lack)-197(of)-204.3(L1)-199.4(expression)-209(in)-200.6(HPV-infected)-203.5(cells)-206.3(\()]TJ 0.85098 0.19216 0.2 scn 21.5118 0 TD (48)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-201.2(Since)-204.5(the)]TJ -22.4693 -1.3858 TD [(protection)-439.6(ef)]TJ /F9 1 Tf 5.2032 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(cacy)-433.6(of)-437.3(HPV)-437.7(vaccines)-433.7(are)-439.7(characterized)-437.2(in)-439.9(clinical)]TJ -5.7386 -1.3921 TD 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276.4912 341.2913 Tm 0.0354 Tc [(an)-9.4(d)]TJ -25.2094 -1.3921 TD 0 Tc (Cervarix)Tj /F13 1 Tf 7.4999 0 0 7.4999 80.4472 332.7873 Tm ()Tj /F8 1 Tf 9 0 0 9 90.4819 328.7622 Tm [(indicated)-498(that)-494.1(the)-495.9(dif)63.1(ferences)-498.8(in)-490.3(antibody)-494.6(Fc-ef)56.9(fector)]TJ -4.5417 -1.3858 TD 0.02 Tc [(func)-4.9(tions)-523.1(m)0.5(ight)-515.8(c)-4.9(o)3.5(ntribute)-521.5(to)-519.4(post-infe)-4.9(c)1.4(tion)-522.5(prote)-4.9(c)1.4(tion)-522.5(\()]TJ 0.85098 0.19216 0.2 scn 25.2032 0 TD 0.0249 Tc (49)Tj 0.15294 0.15294 0.15294 scn 1.0016 0 TD 0.0224 Tc (\).)Tj -26.2047 -1.3921 TD 0.0314 Tc [(Imm)5.6(u)-2.9(ne)-529(correlat)5.8(e)-535.3(o)2.3(f)-528(p)-2.9(rotect)5.8(ion)-530(b)2.3(y)-531.1(H)-2.3(PV)-531.4(vaccination)-530(needs)]TJ 0 -1.3858 TD 0 Tc [(further)-481.3(elucidation)-485(based)-477.9(on)-483.4(more)-478.1(clinical)-483.4(data)-477.2(with)-485.1(functional)]TJ 0 -1.3921 TD [(characteristic)-409.4(of)-405.8(serum)-402.7(or)-408.4(mucosal)-404.9(antibodies,)-406.4(as)-408.4(well)-403.8(as)-402.1(cellular)]TJ 0 -1.3858 TD [(immune)-305.1(responses)-302.1(\()]TJ 0.85098 0.19216 0.2 scn 8.1638 0 TD (50)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -7.5654 -1.3921 TD [(Despi)-10.2(te)-504(the)-502.2(high)-506.6(ef)]TJ /F9 1 Tf 8.2079 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-509.2(again)-8.7(st)-499.4(HPV)-507(infe)-10.1(ction)-507(and)-505.1(HPV-)]TJ -10.2929 -1.3858 TD [(r)-7.7(e)0(l)-8(a)-10.2(ted)-519.5(d)-9.1(ise)-12(a)-10.2(se,)-520.1(l)-8.3(o)0(w)-517.5(vac)-11.8(ci)-16.9(na)-11(ti)-11.2(on)-514.9(co)-10(v)-8.1(era)-17.6(ge)-518.1(of)-512.9(p)-9.1(r)0(o)-11.6(phy)-15.4(la)-12.2(cti)-17.3(c)-510(H)0(P)-13.4(V)]TJ 0 -1.3921 TD [(vaccines)-496.7(still)-501.5(exists.)-493(Particularly,)-503.7(most)-497.6(low-)-493(and)-498.8(middle-income)]TJ 0 -1.3858 TD [(countries)-228.8(incompletely)-225.9(implement)-231.6(HPV)-223.5(vaccination)-225.7(programs)-225.1(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (51)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD [(The)-234.3(high)-229.4(cost,)-228.3(limited)-235.1(supply,)-236.6(and)-228(delivery)-234.3(requirements)-239.4(of)-229.5(the)-231.3(cold)]TJ 0 -1.3858 TD 0.0174 Tc [(chai)-6.1(n)-518.8(m)-2.1(ake)-524.1(i)0.2(t)-518.4(u)2(navai)-6.1(l)2.8(ab)-5.4(le)-517.8(to)-522(peop)-4.3(le)-524.1(in)-518.8(these)-517.8(c)-1.2(ountries)-519.4(\()]TJ 0.85098 0.19216 0.2 scn 25.2094 0 TD 0.0186 Tc (52)Tj 0.15294 0.15294 0.15294 scn 0.9953 0 TD 0.0224 Tc (\).)Tj -26.2047 -1.3921 TD 0 Tc [(Additionally,)-371.8(the)-363.6(biosesafety)-371.2(considerations)-369.3(played)-372.2(a)-363(critical)-369(role)-366.1(in)]TJ 0 -1.3858 TD [(t)-6.7(h)0(e)-520.7(s)-7.7(u)-9.1(c)0(c)-12.1(e)0(s)-13.7(s)-7.7(fu)-14.2(l)-512.2(d)-9.1(ev)-14.2(el)-14.3(op)-13.1(m)-6.9(e)0(n)-13.1(t)-510.6(a)-10.2(n)-7(d)-513.1(d)-9.1(ep)-15.2(lo)-12.2(ym)-8.7(e)-12.3(n)-7(t)-510.6(o)0(f)-519.2(H)-8.5(PV)-523.7(va)-12.1(cc)-12.1(i)-10.9(n)-7(es)-13.7(.)]TJ 0 -1.3921 TD [(Based)-331.9(on)-332.2(high)-330.2(quality)-337(data)-332.3(from)-332.2(very)-332.3(large)-330.1(studies,)-336.8(HPV)-336.9(vaccines)]TJ 0 -1.3858 TD [(exhibit)-330.7(favorable)-334.4(safety)-333.6(pro)]TJ /F9 1 Tf 11.0425 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(les)-330.6(\()]TJ 0.85098 0.19216 0.2 scn 1.7071 0 TD (53)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.548 0 TD (54)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-327.2(The)-335.1(implementation)-333.3(of)-330.3(a)]TJ -15.7417 -1.3921 TD 0.0391 Tc [(robust)-534.5(safety)-536(monitoring)-542.3(s)6.2(y)]TJ 12.7244 0 TD 0.0392 Tc [(ste)-4.6(m)-534.6(f)-3.7(o)3.8(r)-541.7(H)5.5(P)-3.5(V)-536.2(vaccines,)-536.5(which)]TJ -12.7244 -1.3858 TD 0 Tc [(consistently)-344.2(updated)-342.9(data)-344.9(and)-341.4(promptly)-343.3(disclosed)]TJ /F9 1 Tf 20.5417 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(ndings,)-348.4(would)]TJ -21.0709 -1.3921 TD [(en)-13.1(ha)-14.7(n)-7(c)0(e)-516(a)-10.2(cc)-12.1(ur)-10.5(a)-10.2(t)0(e)-516.6(u)-9.1(nd)-9.9(er)-13.7(s)-7.7(t)-6.7(an)-11(d)-9.1(i)0(n)-11.6(g)-512.1(an)-11(d)-513.1(c)0(o)-16.3(m)-6.9(pr)-10.5(eh)-10.5(en)-13.1(s)-7.7(i)0(v)-12.7(e)-516.3(aw)-7.3(a)-10.2(r)-7.7(en)-13.1(es)-13.7(s)]TJ 0 -1.3858 TD [(r)-7.7(e)0(g)-14.2(a)0(r)-11.6(d)-9.1(in)-11.6(g)-512.1(H)0(P)-13.4(V)-512.4(va)-12.1(cc)-12.1(in)-11.6(e)-516.3(s)-7.7(af)-9(et)-12.7(y)-8.1(,)-512.7(m)-6.9(i)0(t)-11.2(i)0(g)-12.7(a)0(t)-10.6(e)-516.3(va)-12.1(cc)-12.1(in)-11.6(e)-516.3(h)0(e)-10.5(s)-7.7(it)-11.2(a)-10.2(n)0(c)-13.1(y)0(,)-514.5(a)-10.2(n)-7(d)]TJ 0 -1.3921 TD [(increase)-307.2(vaccine)-300.1(acceptance)-306.6(and)-303.6(coverage)-301.9(rates.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 304.8944 614.0408 Tm [(3.2)-298.5(Prophylactic)-303.9(HPV)-302.9(vaccines)-304.9(in)]TJ 0 -1.0394 TD [(clinical)-303.1(testing)]TJ /F8 1 Tf 9 0 0 9 318.8409 576.5668 Tm [(There)-323.6(are)-326.3(12)-320.7(high-risk)-319.7(HPV)-324.3(types)-321.1(that)-324.1(are)-320(involved)-319.8(in)-320.2(cancer,)]TJ -1.5496 -1.3921 TD [(including)-246.6(types)-245.5(16,)-247.6(18,)-247.6(31,)-247.6(33,)-247.6(35,)-247.6(39,)-247.6(45,)-241.3(51,)-247.6(52,)-247.6(56,)-247.6(58,)-247.6(and)-246.9(59)-245.1(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (55)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3858 TD [(The)-416.9(Gardasil)-420.6(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 360.8503 555.5338 Tm ()Tj /F8 1 Tf 9 0 0 9 370.2613 551.5652 Tm [(vaccine,)-422.2(which)-419.6(contains)-424.8(the)-420.3(highest)-419.9(number)-418.6(of)]TJ -7.263 -1.3921 TD [(high-risk)-382.7(HPV)-381(serotypes)-384.2(in)-383.2(circulation)-389.1(worldwide,)-385.4(does)-379.5(not)-383(fully)]TJ 0 -1.3858 TD [(cover)-277.5(all)-278.7(high-risk)-281.9(HPV)-273.9(types.)-285.8(To)-271.8(achieve)-284.9(complete)-279.8(protection,)-284.6(the)]TJ 0 -1.3921 TD [(development)-310.4(of)-311.4(prophylactic)-311(HPV)-311.7(vaccines)-314(should)-313.4(further)-311.2(enlarge)]TJ 0 -1.3858 TD [(their)-356.9(protective)-367.2(extent)-364.4(to)-357.1(target)-360.4(more)-364.7(life-threatening)-368(HPV)-362.1(types.)]TJ 0 -1.3921 TD 0.0396 Tc [(The)-539.7(f)-3.3(ollowing)-541.8(se)-4.2(ction)-540.7(w)-1.5(ill)-541.9(s)0.4(um)-5.1(marize)-539.7(the)-539.7(p)-1(r)-5.9(o)4.2(gr)-5.8(ess)-541.3(i)-2.8(n)-540.7(t)1.4(he)]TJ 0 -1.3858 TD 0.044 Tc [(development)-542.2(o)2.3(f)-546.9(p)3.4(rophylactic)-547.9(L)1.8(1-VLP)-5(-)1.1(based)-544.7(H)-2.3(PV)-544(vaccines)]TJ 0 -1.3921 TD 0 Tc [(currently)-299.7(in)-301.4(clinical)-307(trials)-297(\()]TJ 0.85098 0.19216 0.2 scn 10.7906 0 TD [(Table)-302.7(2)]TJ 0.15294 0.15294 0.15294 scn 2.9984 0 TD (\).)Tj -12.2394 -1.3858 TD [(All)-299.6(9-valent)-303.1(HPV)-299.1(vaccines)-301.4(target)-303.7(the)-300.6(same)-301.7(highly)-296.2(carcinogenic)]TJ -1.5496 -1.3921 TD [(H)-8.5(P)-11.2(V)-518.7(t)-13(y)-8.1(p)-15.4(es)-530.2(\()-9.8(H)-8.5(P)-11.2(V)-14.8(-)-11.4(6)0(/)-17.9(1)-12.3(1)-12.3(/)-11.9(16)-18.4(/)-11.9(1)-12.3(8/)-17.9(3)-12.3(1)-12.3(/)-11.9(33)-18.4(/)-11.9(4)-12.3(5/)-17.9(5)-12.3(2)-12.3(/)-11.9(58)-18.4(\))-9.8(.)-525.3(S)-10.7(h)-10.7(a)-10.2(n)-7(g)-14.4(h)-10.7(a)-10.2(i)-521.1(B)-9.1(o)-10.2(v)-8.1(a)-16.5(x)]TJ 0 -1.3858 TD [(Biotechnology)-388.9(Co.,)-385.9(Ltd.)-388(has)-387.7(created)-392(a)-381.9(9-valent)-391.3(HPV)-387.3(vaccine)-388.3(that)]TJ 0 -1.3921 TD [(exhibits)-300.5(high)-305(immunogenicity,)-312.5(good)-302.3(tolerance,)-310(and)-303.6(non-inferiority)]TJ 0 -1.3858 TD [(to)-426.3(Gardasil)-426.9(4)-428.1(i)0(n)-433.6(terms)-425.4(of)-431(both)-428.4(immunogenicity)-436.1(and)-429.5(safety)-428(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (56)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -26.2236 -1.3921 TD [(However,)-361(data)-370.1(regarding)-364.6(other)-362.6(HPV)-368.4(vaccines)-364.4(has)-362.5(not)-364.1(been)-369.5(made)]TJ 0 -1.3858 TD [(public.)-490.8(The)-492.5(11-valent)-498.1(HPV)-494.4(vaccine,)-491.5(developed)-500.5(by)-490.8(the)-489.6(National)]TJ 0 -1.3921 TD [(Vaccine)-275.2(and)-284.7(Serum)-279.8(Institute)-275.7(\(China\),)-280.4(covered)-286.4(two)-272.2(additional)-281.6(HPV)]TJ 0 -1.3858 TD [(types)-289.6(\(HPV-59/68\))-296.6(on)-288.1(top)-290.6(of)-286.2(the)-294.3(commonly)-290.5(used)-290.2(HPV)-292.8(types)-289.6(in)-295.1(9-)]TJ 0 -1.3921 TD [(valent)-487.3(vaccines.)-492.9(The)-486.2(underlying)-497.2(development)-493(strategy)-489.5(might)-484.2(be)]TJ 0 -1.3858 TD [(linked)-220(to)-218.5(the)]TJ /F9 1 Tf 5.1843 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(ndings)-219.9(that)-223.3(HPV-59)-221.7(and)-221.7(68)-219.9(are)-219.2(potentially)-223.8(associated)]TJ -5.7197 -1.3921 TD 0.0506 Tc [(with)-552.3(genital)-549.8(c)-5.8(ancerogenesis)-549.2(\()]TJ 0.85098 0.19216 0.2 scn 13.6504 0 TD 0.0501 Tc (57)Tj 0.15294 0.15294 0.15294 scn 1.0583 0 TD 0.0507 Tc [(\).)-550.2(SC)-5.1(T1000,)-550.2(developed)-550.6(b)2.7(y)]TJ -14.7087 -1.3858 TD 0 Tc [(Sinocelltech)-399.3(Ltd,)-400.6(is)-402.8(a)-400.8(recombinant)-403.9(14-valent)-403.6(L1-VLP-based)-403(HPV)]TJ 0 -1.3921 TD 0.0162 Tc [(vaccine)-519(d)0.8(esigned)-515.8(t)-3.1(o)-510.6(p)-5.5(revent)-513.3(HP)5(V)-521.4(i)5.3(nfection)-513.7(and)-515.8(H)1.4(PV-related)]TJ 0 -1.3858 TD 0 Tc [(cancers.)-399.6(It)-398.1(covers)]TJ /F9 1 Tf 7.5276 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(ve)-398.4(additional)-401.3(HPV)-399.9(types)-403(\(35,)-402.3(39,)-398.8(51,)-398.8(56,)-398.8(and)]TJ -8.0567 -1.3921 TD 0.0168 Tc [(59\))-522.1(c)4.5(omp)-4.9(a)0.3(red)-521.5(w)0.9(ith)-516.8(G)0.4(arda)-6(sil)-520.6(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 425.1967 268.044 Tm 0 Tc ()Tj /F8 1 Tf 9 0 0 9 430.9227 264.0189 Tm 0.0184 Tc [(.)-519.5(S)1.4(CT1000)-516.8(is)-512.1(current)5.4(l)-2.5(y)-512.6(b)1.9(eing)]TJ -14.0032 -1.3858 TD 0 Tc [(investigated)-475.4(in)-477.7(a)-476.4(Phase)-474.2(III)-475(study)-481.7(for)-470.2(HPV)-481.8(infection)-479.3(and)-473.6(HPV-)]TJ 0 -1.3921 TD [(related)-293.4(carcinoma)-302(\(NCT06041061\).)-297.4(A)-295.7(15-valent)-296.6(vaccine)-300.1(developed)]TJ 0 -1.3858 TD [(by)-314.4(Chengda)-321.3(Bio)-313.7(targets)-323.9(HPV-68,)-318.7(in)-320.3(addition)-319.8(to)-313(the)-319.5(14)-314.4(HPV)-324.3(types)]TJ T* [(covered)-210.8(by)-213.6(SCT1000,)-216.1(is)-213.8(currently)-217.8(in)-213.2(development)-215.9(for)-218.2(the)-212.4(prevention)]TJ 0 -1.3921 TD [(of)-298.8(HPV-infected)-304.3(diseases.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 304.8944 164.0692 Tm [(3.3)-298.5(Therapeutic)-306.7(HPV)-298.2(vaccines)-304.9(in)]TJ 0 -1.0441 TD [(clinical)-303.1(testing)]TJ /F8 1 Tf 9 0 0 9 318.8409 126.5386 Tm 0.0245 Tc [(P)-5.6(r)4.2(ophylactic)-523.3(HPV)-525.8(v)-2.5(accin)4.9(e)-0.4(s)-524.9(s)-2.1(carce)5.9(l)-2.7(y)-525.4(e)5.9(radicate)-523.3(preexist)5.2(i)1(ng)]TJ -1.5496 -1.3858 TD 0 Tc [(infe)-10.1(cti)-11(on)-508.6(bec)-9.7(ause)-518.1(L1)-508.1(ca)-10(psi)-8.8(d)-506.8(pro)-8.1(tei)-11(ns)-506(ar)-11.6(e)-503.7(n)-7(ot)-508.2(expr)-14.7(ess)-8.7(ed)-506.5(on)-514.9(the)]TJ 0 -1.3921 TD 0.0241 Tc [(surface)-523.7(o)1.3(f)-522.7(i)0.6(n)4.5(f)0.1(ecte)5.5(d)-526.8(basal)-519.6(epithelial)-519.6(cells)-519(\()]TJ 0.85098 0.19216 0.2 scn 18.463 0 TD 0.0186 Tc (58)Tj 0.15294 0.15294 0.15294 scn 1.0016 0 TD 0.0238 Tc [(\).)-526.7(Therefore,)-520.4(the)]TJ -19.4646 -1.3858 TD 0 Tc [(de)-8.9(v)-8.1(e)0(l)-14.3(o)0(p)-13.1(m)-6.9(en)-13.1(t)-510.6(o)-10.2(f)-509(p)-9.1(r)-7.7(o)0(p)-13.1(h)0(y)-12.6(l)-8.3(ac)-10(t)-6.7(i)-10.9(c)-510(H)-8.5(PV)-517.4(v)-8.1(a)-10.2(cc)-12.1(in)-11.6(es)-523.9(is)-516.2(n)-7(o)0(t)-520.8(a)0(n)-521.2(e)0(f)51.9(f)0(e)-17.4(c)0(t)-12.7(i)0(v)-12.7(e)]TJ 0 -1.3921 TD [(treatment)-460.7(approach)-463.9(for)-457.6(people)-464.6(already)-462.9(infected)-460(with)-459.9(HPV)-462.9(\()]TJ 0.85098 0.19216 0.2 scn 25.2661 0 TD (59)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj ET 0.49804 0.49804 0.49804 scn 49.833 722.494 496.006 27.666 re f 0.63529 0.63529 0.63529 scn 545.726 648.907 0.22681 116.617 re f 49.606 648.907 m 49.606 765.524 l 49.833 765.524 l 49.833 648.907 l 49.606 648.907 l f* 49.833 648.907 496.006 0.28345 re f 545.839 750.16 m 49.833 750.16 l 545.839 750.16 l f* 132.831 722.494 m 49.833 722.494 l 49.833 722.778 l 132.831 722.778 l 132.831 722.494 l f* 132.831 722.494 0.28346 27.666 re f 133.115 722.494 82.715 0.28345 re f 215.83 722.494 0.28345 27.666 re f 216.113 722.494 82.772 0.28345 re f 298.885 722.494 0.22678 27.666 re f 299.112 722.494 82.772 0.28345 re f 381.883 722.494 0.22678 27.666 re f 382.11 722.494 81.751 0.28345 re f 463.861 722.494 0.22678 27.666 re f 464.088 722.494 81.751 0.28345 re f 132.831 649.19 0.28346 73.304 re f 215.83 649.19 0.28345 73.304 re f 298.885 649.19 0.22678 73.304 re f 381.883 649.19 0.22678 73.304 re f 463.861 649.19 0.22678 73.304 re f 49.833 749.934 496.006 0.45355 re f /Cs6 cs 1 1 1 scn 49.606 750.387 0.22676 19.502 re f 545.839 750.387 0.28345 19.502 re f /Cs6 cs 1 1 1 scn 49.606 750.387 4.989 19.502 re f 39.628 750.387 14.967 19.502 re f 541.077 750.387 5.0457 19.502 re f 541.077 750.387 15.024 19.502 re f 39.628 750.387 516.472 9.978 re f BT /F5 1 Tf 6.9999 0 0 6.9999 49.6063 760.3652 Tm 0.49804 0.49804 0.49412 scn [(TABLE)-306.1(1)-794(Continued)]TJ /F1 1 Tf 9 0 0 9 75.1748 738.3116 Tm 1 1 1 scn (Valency)Tj -1.285 -1.1087 TD [(\(Brand)-303.8(name\))]TJ 10.7969 1.1087 TD (2vHPV)Tj -0.9323 -1.1087 TD (\(Cervarix)Tj 6.0001 0 0 6.0001 189.0708 730.8282 Tm ()Tj 9 0 0 9 193.9464 728.3337 Tm (\))Tj 5.5181 1.1087 TD (4vHPV)Tj -0.8756 -1.1087 TD (\(Gardasil)Tj 6.0001 0 0 6.0001 271.729 730.8282 Tm ()Tj 9 0 0 9 276.6047 728.3337 Tm (\))Tj 5.5622 1.1087 TD (9vHPV)Tj -1.3291 -1.1087 TD [(\(Gardasil)-307.3(9)]TJ 6.0001 0 0 6.0001 358.7527 730.8282 Tm ()Tj 9 0 0 9 363.6282 728.3337 Tm (\))Tj 5.0709 1.1087 TD (2vHPV)Tj -0.8 -1.1087 TD (\(Cecolin)Tj 6.0001 0 0 6.0001 436.3652 730.8282 Tm ()Tj 9 0 0 9 441.2408 728.3337 Tm (\))Tj 5.5622 1.1087 TD (2vHPV)Tj -1.3354 -1.1087 TD (\(WalrinVax)Tj 6.0001 0 0 6.0001 523.162 730.8282 Tm ()Tj 9 0 0 9 528.0376 728.3337 Tm (\))Tj /F8 1 Tf 6.9999 0 0 6.9999 78.0094 683.5463 Tm 0.15294 0.15294 0.15294 scn (Ef)Tj /F9 1 Tf 0.8585 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(cacy)-305.9(*)]TJ 7.759 1.3526 TD [(VE)-304.2(against)-303(HPV-16/18)]TJ 0.2025 -1.3526 TD [(incident)-307.7(infection)-304(was)]TJ 2.2597 -1.3607 TD [(66.8%)-300.2(\(40\))]TJ 9.7514 5.4264 TD [(100%)-299.5(ef)]TJ /F9 1 Tf 3.1992 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-297.8(against)]TJ -3.264 -1.3526 TD [(HPV)-305.5(16/18-related)]TJ -0.6236 -1.3607 TD [(cervical)-303.7(intraepithelial)]TJ 0.0405 -1.3526 TD [(neoplasia)-300.4(and)-300(ef)]TJ /F9 1 Tf 6.536 0 TD ()Tj /F8 1 Tf 0.5264 0 TD (cacy)Tj -7.3054 -1.3607 TD [(against)-303(HPV)-305.5(persistent)]TJ 2.1463 -1.3607 TD [(infection)-304(for)]TJ -0.5831 -1.3526 TD [(78)-200.2(months)-295(\(41\))]TJ 9.8809 8.1396 TD [(At)-298.8(1)-298.5(month)-302.7(post-Dose)-300.3(3,)]TJ 0.3159 -1.3526 TD [(>99%)-302.3(of)-302.4(participants)-306.7(in)]TJ 1.4578 -1.3607 TD [(the)-298(per-protocol)]TJ 0 -1.3526 TD (immunogenicity)Tj -1.8385 -1.3607 TD [(population)-299(seroconverted)]TJ 0.8828 -1.3607 TD [(to)-299.5(each)-297.7(vaccine)-303.8(HPV)]TJ 2.4135 -1.3526 TD [(type)-296.4(\(42\))]TJ 9.4922 6.7871 TD [(Vaccine)-299.7(ef)]TJ /F9 1 Tf 4.1954 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(cacy)-305.9(was)]TJ -5.5722 -1.3607 TD [(100%)-299.5(against)-303(high-grade)]TJ -0.1215 -1.3526 TD [(genital)-300.4(lesions)-301.8(and)-308.1(97.3%)]TJ 1.6036 -1.3607 TD [(against)-311.1(persistent)]TJ 0.7451 -1.3607 TD [(infection)-304(\(43\))]TJ 11.2416 5.4345 TD [(100%)-307.6(in)-300.5(postive)]TJ -1.5955 -1.3607 TD [(seropositive)-305.7(at)-297.7(Month)-302.5(7)]TJ 0.1944 -1.3526 TD [(in)-300.5(two-)-297.1(and)-308.1(three-dose)]TJ 1.4497 -1.3607 TD [(regimens)-297.2(for)-302.9(all)]TJ -0.1782 -1.3607 TD [(participants)-306.7(\(34\))]TJ 6.5001 0 0 6.5001 49.6063 640.403 Tm [(*,)-302.8(Protection)-302.5(rate)-303.8(for)-301.5(precancerous)-307.9(lesions)-296.5(or)-304.7(high-grade)-302.2(genital)-301.4(lesions)-305.3(caused)-301.1(by)-306.7(HPV)-301(infection.)]TJ /F1 1 Tf 6.9999 0 0 6.9999 49.6063 800.9573 Tm 0.49804 0.49804 0.49412 scn [(Wang)-305.1(et)-300.8(al.)]TJ 57.1394 0 TD (10.3389/fimmu.2024.1362770)Tj -57.1394 -109.3302 TD [(Frontiers)-304.6(in)]TJ 0.85098 0.19216 0.2 scn 5.5074 0 TD (Immunology)Tj 58.8564 0 TD (frontiersin.org)Tj 0.15294 0.15294 0.15294 scn -29.5213 0 TD (04)Tj ET endstream endobj 80 0 obj<> endobj 81 0 obj<> endobj 82 0 obj<> endobj 83 0 obj<> endobj 84 0 obj<> endobj 85 0 obj<> endobj 86 0 obj<> endobj 87 0 obj<> endobj 88 0 obj<> endobj 89 0 obj<> endobj 90 0 obj<> endobj 91 0 obj<> endobj 92 0 obj<> endobj 93 0 obj<> endobj 94 0 obj<> endobj 95 0 obj<> endobj 96 0 obj<> endobj 97 0 obj<> endobj 98 0 obj<> endobj 99 0 obj<> endobj 100 0 obj<> endobj 101 0 obj<> endobj 102 0 obj<> endobj 103 0 obj<> endobj 104 0 obj<> endobj 105 0 obj<> endobj 106 0 obj<> endobj 107 0 obj<> endobj 108 0 obj<> endobj 109 0 obj<> endobj 110 0 obj<> endobj 111 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 112 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 113 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 114 0 obj<>/Font<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 115 0 obj<>stream /GS1 gs BT /F8 1 Tf 9 0 0 9 49.6063 333.1842 Tm /Cs6 cs 0.15294 0.15294 0.15294 scn 0 Tc 0 Tw [(Cellular)-208.2(immune)-216.9(responses)-207.7(to)-212.2(HPV)-210.9(antigens)-208.5(play)-212.2(important)-207.6(roles)-209.9(in)]TJ 0 -1.3921 TD 0.0207 Tc [(vi)3.5(ral)-516.7(c)-4.2(l)6.1(e)-4.2(a)4.2(r)0.4(ance)-520.8(and)-517.6(a)-2.1(nti)3.5(c)2.1(ancer)-516.1(i)]TJ 13.9969 0 TD 0.0199 Tc [(mmune)-521.6(responses.)-518(Inef)58.9(fective)]TJ -13.9969 -1.3858 TD 0 Tc [(ce)-12.1(ll)-10.2(ul)-11.1(ar)-515.5(im)-11.5(mu)-9.7(n)-7(e)-510(res)-15(pon)-13.8(s)-7.7(e)0(s)-517.6(t)0(o)-514.5(HPV)-15.6(-16)-514.8(E)-11.2(2)0(,)-512.4(E)0(6)-11(,)-512.7(or)-509.2(E)-11.2(7)-510(pe)-8.9(pt)-9.5(id)-13.7(es)]TJ 0 -1.3921 TD [(involve)-417.8(infection)-416.3(persistence)-421(or)-414.7(disease)-423(progression)-419.8(in)-414.7(low-grade)]TJ 0 -1.3858 TD [(intrae)-10.7(pitheli)-12.2(al)-503.5(lesion)-509.9(\(LSIL\))-506.1(patie)-11.4(nts)-506.4(\()]TJ 0.85098 0.19216 0.2 scn 15.9685 0 TD (60)Tj 0.15294 0.15294 0.15294 scn 0.9638 0 TD [(\).)-503.6(HPV-16)-511.5(E6)-502.3(and)-505.1(E7-)]TJ -16.9323 -1.3858 TD 0.0133 Tc (speci)Tj /F9 1 Tf 2.0409 0 TD 0 Tc ()Tj /F8 1 Tf 0.5417 0 TD 0.0131 Tc [(c)-515.8(cellular)-517.4(i)2.2(mmune)-509.5(responses)-511.1(f)1.7(acilitate)-509.5(t)0.1(he)-509.5(regression)-516.8(of)]TJ -2.5827 -1.3921 TD 0.0182 Tc [(HPV-16-associated)-513.8(lesion)4.9(s)-518.6(\()]TJ 0.85098 0.19216 0.2 scn 12.2142 0 TD 0.0186 Tc (61)Tj 0.15294 0.15294 0.15294 scn 0.9953 0 TD 0.0173 Tc [(\).)-520.6(Similarly,)-520.6(t)4.3(h)0.3(e)-517.9(p)-4.4(ercentages)-519.5(o)0.8(f)]TJ -13.2094 -1.3858 TD 0 Tc (IFN-)Tj /F14 1 Tf 1.9528 0 TD (g)Tj /F8 1 Tf 0.9071 0 TD [(positi)-11.3(ve)-499.2(enzyme-)-13.7(linked)-509.8(immun)-9.3(ospot)-503.7(\(ELISpo)-12.3(t\))-501.5(res)-8.7(ponses)]TJ -2.8598 -1.3921 TD [(to)-401.1(HPV-16)-398.1(E6)-401.5(and)-398.1(E7)-401.5(are)-401.9(signi)]TJ /F9 1 Tf 13.2157 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cantly)-405.4(increased)-404.5(among)-395.3(women)]TJ -13.7449 -1.3858 TD [(with)-346.5(recently)-351.9(resolved)-352.9(HPV)-349.5(infection)-347(versus)-354.9(those)-343.7(with)-352.8(persistent)]TJ 0 -1.3921 TD [(HPV-16)-303.6(infection)-302.9(in)-301.4(the)-300.6(cervix)-301.4(\()]TJ 0.85098 0.19216 0.2 scn 13.1465 0 TD (62)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -12.548 -1.3858 TD [(Th)-7.7(era)-11.3(pe)-8.9(ut)-9.5(ic)-508.2(H)-8.5(P)0(V)-511.1(vac)-11.8(ci)-10.6(nes)-512.1(ar)-11.6(e)-503.7(d)-9.1(ev)-7.9(el)-8(oped)-519.6(to)-508.2(st)-8(imu)-14.3(late)-516.2(ce)-12.1(ll-)]TJ -1.5559 -1.3921 TD 0.0307 Tc [(me)5.8(diat)5.1(ed)-526.5(immunit)5.1(y)-531.8(f)6.7(o)1.6(r)-531.3(t)-1.2(he)-523.4(clearan)4.8(c)-0.5(e)-529.7(o)1.6(f)-528.7(i)0.9(nf)6.7(ection)-524.4(\()]TJ 0.85098 0.19216 0.2 scn 23.3827 0 TD 0.0312 Tc (63)Tj 0.15294 0.15294 0.15294 scn 1.0205 0 TD 0 Tc (,)Tj 0.85098 0.19216 0.2 scn 0.7748 0 TD 0.0312 Tc (64)Tj 0.15294 0.15294 0.15294 scn 1.0205 0 TD 0.0287 Tc (\).)Tj -26.1984 -1.3858 TD 0 Tc [(Among)-309.1(HPV)-311.7(early)-304.9(proteins)-310.9(\(E1,)-312.9(E2,)-309.5(E6,)-309.5(and)-309.9(E7\))-304.2(and)-309.9(late)-308.4(proteins)]TJ 0 -1.3921 TD [(\(L1,)-356.5(L2\),)-356.5(HPV)-355.8(E6)-351.1(and)-354(E7)-357.4(proteins)-355(are)-357.8(constitutively)-358(expressed)-359.8(in)]TJ 0 -1.3858 TD [(both)-371.7(premalignant)-381.6(and)-372.9(invasive)-377.6(lesions)-379(and)-372.9(play)-375.9(key)-375.6(roles)-373.7(in)-376.9(the)]TJ 0 -1.3921 TD [(development)-348.2(of)-349.2(malignancy)-347.4(\()]TJ 0.85098 0.19216 0.2 scn 11.9433 0 TD (65)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-346.1(Further,)-349.2(E6)-351.1(and)-347.7(E7)-344.8(can)-344.6(activate)]TJ -12.9008 -1.3858 TD (antigen-speci)Tj /F9 1 Tf 5.2913 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(c)-402.9(CD8)]TJ 6.7499 0 0 5.9992 126.1417 124.6677 Tm (+)Tj 9 0 0 9 133.6818 120.6992 Tm [(or)-402.1(CD4)]TJ 6.7499 0 0 5.9992 161.8582 124.6677 Tm (+)Tj 9 0 0 9 169.3417 120.6992 Tm [(T)-406.5(cells)-401.6(and)]TJ /F9 1 Tf 5.0205 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(nally)-407.3(evoke)-404.4(cellular)]TJ -18.8535 -1.3921 TD [(immune)-506.7(response)-11(s)-499(\()]TJ 0.85098 0.19216 0.2 scn 8.5732 0 TD (66)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9575 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (68)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-503.6(Therefore)-12.4(,)-500.1(E)0(6)-502.3(and)-498.8(E7)-502.3(pro)-8.1(teins)-504.4(are)]TJ -10.9984 -1.3858 TD 0.0136 Tc [(conside)-5(r)-0.4(ed)-518.4(ideal)-511.2(a)-2.9(ntigens)-516.9(f)2.2(or)-516.9(the)-5(r)-0.4(apeutic)-515.3(H)-1.2(PV)-517.7(vac)-5(c)1.3(in)-6(es.)-511.7(T)-2.3(LR)]TJ 0 -1.3921 TD 0 Tc [(agonists)-471.6(alone)-470.2(or)-471.4(mixed)-472(with)-472.5(other)-469.7(components)-473.8(are)-471.2(commonly)]TJ 0 -1.3858 TD [(tested)-420.1(adjuvants)-416.6(for)-413.5(therapeutic)-423(HPV)-412.5(vaccines)-421.1(\()]TJ 0.85098 0.19216 0.2 scn 19.9685 0 TD (69)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9575 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (72)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-415.4(Recently)]TJ 5.9717 29.1654 TD 0.0233 Tc [(dev)-3.7(e)-1.6(lo)-5.8(ped)-527.6(n)-2.6(ew)-528(adj)-3.9(u)-4.7(va)-5.8(nts,)-527.2(such)-529.2(as)]TJ /F14 1 Tf 15.6472 0 TD 0 Tc (a)Tj /F8 1 Tf 0.6488 0 TD 0.0245 Tc [(-G)-4.5(alactosylceramid)-3.5(e)-523.3(\()]TJ /F14 1 Tf 9.4866 0 TD 0 Tc (a)Tj /F8 1 Tf 0.6488 0 TD (-)Tj -26.4315 -1.3921 TD [(Ga)-7.8(lC)-7.4(er\))-10.8(,)-512.7(man)-11.6(gan)-12.8(ese)-517.4(\(Mn)-13.7(4)]TJ 6.7499 0 0 5.9992 405.3542 324.6803 Tm (+)Tj 9 0 0 9 409.2661 320.6551 Tm [(\)-)-8.5(dop)-9.6(ed)-512.8(s)-7.7(ili)-11.1(ca)-513.9(na)-11(nopa)-17.7(rt)-8(icl)-12.6(es)-511.3(\(Mn)-13.7(4)]TJ 6.7499 0 0 5.9992 538.866 324.6803 Tm (+)Tj 9 0 0 9 542.7778 320.6551 Tm (-)Tj -26.4315 -1.3858 TD 0.02 Tc [(SNPs\),)-524.2(and)-524.6(v)-0.7(ery)-523.6(s)-0.3(mall-size)]TJ 12.3654 0 TD 0.0221 Tc [(pro)5.6(t)-3.5(eol)7.5(i)-1.4(po)5.6(so)5.6(mes)-514.7(\()-0.3(VSSP\))-516.8(\()]TJ 0.85098 0.19216 0.2 scn 11.3071 0 TD 0.0186 Tc (73)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 1.0016 0 TD 0 Tc ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5291 0 TD 0.0186 Tc (75)Tj 0.15294 0.15294 0.15294 scn 0.9953 0 TD 0.0224 Tc (\),)Tj -26.1984 -1.3921 TD 0.039 Tc [(might)-540.9(p)-1.6(lay)-542.4(r)-0.2(oles)-541.9(in)-541.3(reinforcing)-536.1(t)0.8(he)-534(ef)]TJ /F9 1 Tf 17.5055 0 TD 0 Tc ()Tj /F8 1 Tf 0.5732 0 TD 0.039 Tc [(cacy)-536.1(of)-539.3(the)-4.8(r)-0.2(apeutic)]TJ -18.0787 -1.3858 TD 0 Tc [(HPV)-299.1(vaccines.)]TJ 1.5496 -1.3858 TD [(Prophylac)-12.4(tic)-502.3(HPV)-500.7(vaccine)-10.3(s)-499(are)-502.7(mainly)-505(protein-b)-9.9(ased)-505.5(VLPs.)]TJ -1.5496 -1.3921 TD [(Therapeutic)-470.1(HPV)-469.2(vaccines)-471.5(are)-471.2(primarily)-476.5(based)-465.3(on)-470.8(nucleic)-475.5(acid,)]TJ 0 -1.3858 TD [(bacterial/viral)-334.8(vector,)-330.7(protein/peptide)-334.3(or)-332.9(whole)-328.3(cells)-332.3(\()]TJ 0.85098 0.19216 0.2 scn 21.5937 0 TD (76)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-333.5(To)-328.5(date,)]TJ -22.5512 -1.3921 TD [(no)-313.3(therapeutic)-322.3(HPV)-318(vaccine)-319(has)-318.4(been)-319.1(licensed.)-321.8(Safety)-324(pro)]TJ /F9 1 Tf 23.4079 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(les)-318(and)]TJ -23.937 -1.3858 TD [(vaccine)-224.5(ef)]TJ /F9 1 Tf 3.8173 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-225.7(for)-224.5(therapeutic)-227.8(HPV)-229.8(vaccines)-225.8(tested)-231.2(in)-219.5(clinical)-231.4(trials)]TJ -4.3465 -1.3921 TD 0.0111 Tc [(a)11.1(r)-6.8(e)-505.2(s)-2.9(umm)4.2(a)0.8(rized)-508.3(in)]TJ 0.85098 0.19216 0.2 scn 8.6173 0 TD 0.0096 Tc [(Table)-513(3)]TJ 0.15294 0.15294 0.15294 scn 3.263 0 TD 0.0129 Tc [(.)-512.4(A)-503.2(com)6(p)3.8(le)12.9(t)-6.1(e)-503.4(re)12.9(g)-7.6(r)5.2(essi)12.9(on)-510.7(of)-502.4(le)12.9(s)-7.1(i)2(o)12.9(n)-4.4(s)]TJ -11.8803 -1.3858 TD 0 Tc [(triggered)-379(by)-377.4(therapeutic)-385.2(HPV)-381(vaccines)-383.3(has)-375.1(been)-382.1(reported,)-380(with)-384.3(a)]TJ 0 -1.3921 TD [(regression)-249(rate)-251.1(ranging)-248.1(from)-250.3(17.4%)-246.9(to)-250(89.4%)-246.9(in)-251(female)-250.4(patients)-253.3(\()]TJ 0.85098 0.19216 0.2 scn 25.6063 0 TD (54)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn -26.5638 -1.3858 TD (78)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (81)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (82)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (84)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9575 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (86)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (88)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5291 0 TD (89)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\).)-308.3(The)-309.9(clearance)-319.6(of)-305.1(HPV)-311.7(DNA)-314.3(in)-307.7(infected)]TJ -9.8583 -1.3921 TD [(cells)-256.7(is)-264.2(considered)-268.8(a)-262.2(predictor)-262.4(of)-261(vaccine)-268.6(ef)]TJ /F9 1 Tf 16.9575 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(cacy,)-259.7(as)-263.6(the)-262.8(presence)-263.5(of)]TJ -17.4929 -1.3858 TD [(HPV)-223.5(DNA)-219.8(at)-224.8(the)-225(cervical)-220.8(site)-226.5(is)-220.1(often)-224(associated)-229.6(with)-220.5(histologic)-228.3(and)]TJ 0 -1.3921 TD [(cytological)-332.5(changes)-339.3(in)-332.9(cervical)-334.2(intraepithelial)-337.4(neoplasia)-338(\(CIN\))-338.7(\()]TJ 0.85098 0.19216 0.2 scn 25.6063 0 TD (77)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn -26.5638 -1.3858 TD (79)Tj /F12 1 Tf 0.15294 0.15294 0.15294 scn 0.9575 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5102 0 TD (81)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (83)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5228 0 TD (87)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (90)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (\).)Tj -5.3039 -1.3921 TD 0.011 Tc [(In)-512.6(addition,)-508(v)-3.4(acc)11(i)-5.9(ne)-511.6(antigen-speci)]TJ /F9 1 Tf 14.5197 0 TD 0 Tc ()Tj /F8 1 Tf 0.5417 0 TD 0.0114 Tc [(c)-511.2(T)1.8(-cell)-507.1(r)-2.6(e)11.4(s)-8.6(ponses)-506.5(were)]TJ -16.611 -1.3858 TD 0.0585 Tc [(compr)-5.9(e)2.1(hen)-5.2(s)0.5(ivel)-6.5(y)-554.4(e)-4.2(valuate)-4.2(d)-1(.)-561.3(I)0.9(n)-559.5(a)-562.8(P)-3.1(h)3.7(ase)-564.9(I)-559.7(tr)-5.9(ial,)-561.3(A)-4.1(M)-1.4(V00)-4.2(2)]TJ 0 -1.3921 TD 0.0282 Tc [(vaccination)-526.9(i)-1.6(nduced)-529(E6)-525.9(and/o)5.4(r)-533.8(E7)-532.2(speci)]TJ /F9 1 Tf 18.085 0 TD 0 Tc ()Tj /F8 1 Tf 0.5606 0 TD 0.029 Tc [(c)-525.1(cellular)-526.7(i)-0.8(mmune)]TJ -18.6457 -1.3858 TD 0 Tc [(response)-338.6(in)-332.9(83.3%)-341.4(subjects)-338.8(\()]TJ 0.85098 0.19216 0.2 scn 11.515 0 TD (78)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD 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(System)Tj 6.2488 0.5543 TD [(Adjuvant)-1715.2(Sponsor)-1986.7(Indications)]TJ 18.7591 1.1087 TD (Ef)Tj /F10 1 Tf 0.9071 0 TD ()Tj /F1 1 Tf 0.5795 0 TD (cacy)Tj -0.5417 -1.1087 TD (and)Tj -1.4614 -1.1087 TD (outcomes)Tj 6.1732 1.1087 TD (Phase)Tj 4.0567 0.5543 TD (ClinicalTrials.gov)Tj 1.8142 -1.1087 TD (Identi)Tj /F10 1 Tf 2.6142 0 TD ()Tj /F1 1 Tf 0.5795 0 TD (er)Tj 3.9874 0.5543 TD (Ref.)Tj /F8 1 Tf 6.9999 0 0 6.9999 55.2756 692.4471 Tm 0.15294 0.15294 0.15294 scn (HPV-6/11/16/18/)Tj 0.4698 -1.3606 TD (31/33/45/52/58)Tj 1.0772 -1.3526 TD (\(9-valent\))Tj 10.3912 1.3526 TD [(N.)-298.4(A.)-6327.5(N.)-306.5(A.)]TJ 14.4569 2.7132 TD [(Instituto)-301.7(de)]TJ -0.3159 -1.3526 TD (Investigacio)Tj /F15 1 Tf 4.6651 0.0405 TD ()Tj /F8 1 Tf 0.081 -0.0405 TD (n)Tj -3.7985 -1.3606 TD (Hospital)Tj -0.9314 -1.3526 TD (Universitario)Tj 1.2878 -1.3607 TD [(La)-303.6(Paz)]TJ 6.5198 4.7542 TD [(HPV)-297.4(infection;)]TJ 1.8466 -1.3607 TD (HPV-)Tj -0.2916 -1.3526 TD (Related)Tj -0.8423 -1.3607 TD (Carcinoma.)Tj 9.808 2.0329 TD [(N.A.)-5265.3(IV)-5012(NCT05439083)-3870(N.A.)]TJ -44.4237 -5.7585 TD (HPV-6/11/16/18/)Tj 0.4698 -1.3607 TD (31/33/45/52/58)Tj 1.0772 -1.3607 TD (\(9-valent\))Tj 10.3912 1.3607 TD [(N.)-298.4(A.)-6327.5(N.)-306.5(A.)]TJ 13.5822 1.3607 TD [(Shanghai)-297.6(Bovax)]TJ 0.3483 -1.3607 TD (Biotechnology)Tj 1.1258 -1.3607 TD [(Co.,)-295.1(Ltd.)]TJ 6.6899 3.3935 TD [(HPV)-297.4(Infections;)]TJ 2.0653 -1.3526 TD (HPV-)Tj -0.2916 -1.3607 TD (Related)Tj -0.8423 -1.3526 TD (Carcinoma.)Tj 7.6213 4.0658 TD [(Non-inferior)-304.7(to)]TJ 0.5102 -1.3526 TD [(Gardasil)-304.7(4)-298.5(i)0(n)]TJ -0.6722 -1.3607 TD (immunogenicity)Tj 1.2473 -1.3526 TD [(and)-300(safety)]TJ 8.2449 2.0329 TD [(III)-5026.8(NCT04895020)-3983.4(\()]TJ 0.85098 0.19216 0.2 scn 16.1902 0 TD (56)Tj 0.15294 0.15294 0.15294 scn 0.9638 0 TD (\))Tj -68.7211 -6.4388 TD (HPV-6/11/16/18/)Tj 0.4698 -1.3606 TD (31/33/45/52/58)Tj 1.0772 -1.3607 TD (\(9-valent\))Tj 10.3912 1.3607 TD [(N.)-298.4(A.)-6327.5(N.)-306.5(A.)]TJ 13.971 2.0329 TD [(Weill)-302(Medical)]TJ 0.7937 -1.3526 TD [(College)-301.8(of)]TJ 0.5345 -1.3606 TD (Cornell)Tj -0.5912 -1.3526 TD (University)Tj 7.5646 5.4264 TD [(HPV)-305.5(Positive)]TJ -0.2835 -1.3606 TD (Oropharyngeal)Tj 0.0081 -1.3526 TD [(Squamous)-299.3(Cell)]TJ 0.6803 -1.3606 TD (Carcinoma;)Tj -1.0448 -1.3526 TD (HIV-1-infection;)Tj 0.2916 -1.3607 TD [(HPV)-305.5(Infection.)]TJ 10.5613 3.3935 TD [(N.A.)-5281.5(III)-5026.8(NCT04255849)-3870(N.A.)]TJ -44.4237 -5.7666 TD (HPV-6/11/16/18/)Tj 0.3078 -1.3526 TD (31/33/45/52/58/)Tj 2.0815 -1.3607 TD (59/68)Tj -1.0772 -1.3526 TD (\(11-valent\))Tj /F11 1 Tf 7.2082 2.0329 TD (Hansenulapolymorpha)Tj /F8 1 Tf 11.9057 0 TD [(N.)-306.5(A.)]TJ 6.5684 2.0329 TD (National)Tj -0.7613 -1.3526 TD [(Vaccine)-299.7(and)]TJ 1.1987 -1.3607 TD (Serum)Tj -1.8547 -1.3526 TD [(Institute,)-305.4(China)]TJ 8.3259 4.0658 TD [(HPV)-297.4(infection;)]TJ 1.8466 -1.3526 TD (HPV-)Tj -0.2916 -1.3607 TD (Related)Tj -0.8423 -1.3526 TD (Carcinoma.)Tj 9.808 2.0329 TD [(N.A.)-5281.5(III)-5026.8(NCT05262010)-3870(N.A.)]TJ -44.4237 -4.4059 TD (HPV-6/11/16/18/)Tj 0.3078 -1.3607 TD (31/33/35/39/45/)Tj 0.162 -1.3525 TD (51/52/56/58/59)Tj 0.899 -1.3607 TD (\(14-valent,)Tj -1.3688 -1.3607 TD [(named)-303.1(SCT1000\))]TJ 10.8285 2.7213 TD [(Insect)-308.9(cells)]TJ 8.3016 2.0329 TD (Aluminum-)Tj 0.1377 -1.3606 TD (phosphate-)Tj 1.1258 -1.3526 TD (based)Tj -0.6155 -1.3607 TD (adjuvant)Tj 6.5603 2.7132 TD (Sinocelltech)Tj 1.6036 -1.3526 TD (Ltd.)Tj 5.961 2.7132 TD [(HPV)-297.4(infection;)]TJ 1.8466 -1.3606 TD (HPV-)Tj -0.2916 -1.3526 TD (Related)Tj -0.8423 -1.3607 TD (Carcinoma.)Tj 9.808 2.041 TD [(N.A.)-5281.5(III)-5026.8(NCT06041061)-3870(N.A.)]TJ -44.4237 -7.1272 TD (HPV-6/11/16/18/)Tj 0.3078 -1.3526 TD (31/33/35/39/45/)Tj 0 -1.3607 TD (51/52/56/58/59/)Tj 2.7213 -1.3526 TD (68)Tj -1.717 -1.3607 TD (\(15-valent\))Tj /F11 1 Tf 8.658 2.7132 TD [(Escherichia)-303.2(coli)]TJ /F8 1 Tf 10.456 0 TD [(N.)-306.5(A.)]TJ 5.0782 4.7542 TD [(Liaoning)-303(Cheng)]TJ 2.6403 -1.3607 TD (Da)Tj -2.2759 -1.3607 TD (Biotechnology)Tj 1.1258 -1.3526 TD [(Co.,)-295.1(Ltd;)]TJ -1.1501 -1.3607 TD [(Beijing)-301.6(Health)]TJ 1.6036 -1.3526 TD (Guard)Tj -1.5793 -1.3606 TD (Biotechnology)Tj 2.0977 -1.3526 TD (Inc.)Tj 5.9367 6.779 TD [(HPV)-297.4(infection;)]TJ 1.8466 -1.3526 TD (HPV-)Tj -0.2916 -1.3607 TD (Related)Tj -0.8423 -1.3526 TD (Carcinoma.)Tj 9.808 2.0329 TD (N.A.)Tj 6.9999 0 0 6.9999 413.4046 409.9464 Tm (IND)Tj -0.9638 -1.3607 TD (Approval)Tj 10.1563 0.6803 TD [(/)-6627.1(N.A.)]TJ 6.5001 0 0 6.5001 49.6063 357.3354 Tm [(N.A.,)-301(not)-305.4(available.)]TJ /F1 1 Tf 6.9999 0 0 6.9999 49.6063 800.9573 Tm 0.49804 0.49804 0.49412 scn [(Wang)-305.1(et)-300.8(al.)]TJ 57.1394 0 TD (10.3389/fimmu.2024.1362770)Tj -57.1394 -109.3302 TD [(Frontiers)-304.6(in)]TJ 0.85098 0.19216 0.2 scn 5.5074 0 TD (Immunology)Tj 58.8564 0 TD (frontiersin.org)Tj 0.15294 0.15294 0.15294 scn -29.5051 0 TD (05)Tj ET endstream endobj 116 0 obj<> 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0.28345 re f 403.37 505.927 0.22678 26.135 re f 403.597 505.927 49.096 0.28345 re f 452.693 505.927 0.28345 26.135 re f 452.976 505.927 46.715 0.28345 re f 499.691 505.927 0.28345 26.135 re f 499.975 505.927 45.751 0.28345 re f 100.517 470.324 m 49.833 470.324 l 49.833 470.608 l 100.516 470.608 l 100.516 470.324 l f* 100.517 470.324 m 100.517 505.927 l 100.743 505.927 l 100.743 470.324 l 100.517 470.324 l f* 100.743 470.324 55.786 0.28345 re f 156.529 470.324 m 156.529 505.927 l 156.756 505.927 l 156.756 470.324 l 156.529 470.324 l f* 156.756 470.324 45.808 0.28345 re f 202.564 470.324 m 202.564 505.927 l 202.79 505.927 l 202.79 470.324 l 202.564 470.324 l f* 248.315 470.324 m 202.79 470.324 l 202.79 470.608 l 248.315 470.608 l 248.315 470.324 l f* 248.315 470.324 m 248.315 505.927 l 248.542 505.927 l 248.542 470.324 l 248.315 470.324 l f* 248.542 470.324 54.822 0.28345 re f 303.364 470.324 m 303.364 505.927 l 303.59 505.927 l 303.59 470.324 l 303.364 470.324 l f* 303.59 470.324 99.78 0.28345 re f 403.37 470.324 m 403.37 505.927 l 403.597 505.927 l 403.597 470.324 l 403.37 470.324 l f* 403.597 470.324 49.096 0.28345 re f 452.693 470.324 m 452.693 505.927 l 452.976 505.927 l 452.976 470.324 l 452.693 470.324 l f* 452.976 470.324 46.715 0.28345 re f 499.691 470.324 m 499.691 505.927 l 499.975 505.927 l 499.975 470.324 l 499.691 470.324 l f* 499.975 470.324 45.751 0.28345 re f 100.517 425.253 m 49.833 425.253 l 49.833 425.48 l 100.516 425.48 l 100.516 425.253 l f* 100.517 425.253 0.22676 45.071 re f 100.743 425.253 55.786 0.22678 re f 156.529 425.253 0.22678 45.071 re f 156.756 425.253 45.808 0.22678 re f 202.564 425.253 0.22678 45.071 re f 248.315 425.253 m 202.79 425.253 l 202.79 425.48 l 248.315 425.48 l 248.315 425.253 l f* 248.315 425.253 0.22676 45.071 re f 248.542 425.253 54.822 0.22678 re f 303.364 425.253 0.22675 45.071 re f 303.59 425.253 99.78 0.22678 re f 403.37 425.253 0.22678 45.071 re f 403.597 425.253 49.096 0.22678 re f 452.693 425.253 0.28345 45.071 re f 452.976 425.253 46.715 0.22678 re f 499.691 425.253 0.28345 45.071 re f 499.975 425.253 45.751 0.22678 re f 100.517 361.134 m 49.833 361.134 l 49.833 361.417 l 100.516 361.417 l 100.516 361.134 l f* 100.517 361.134 0.22676 64.12 re f 100.743 361.134 55.786 0.28345 re f 156.529 361.134 0.22678 64.12 re f 156.756 361.134 45.808 0.28345 re f 202.564 361.134 0.22678 64.12 re f 248.315 361.134 m 202.79 361.134 l 202.79 361.417 l 248.315 361.417 l 248.315 361.134 l f* 248.315 361.134 0.22676 64.12 re f 248.542 361.134 54.822 0.28345 re f 303.364 361.134 0.22675 64.12 re f 303.59 361.134 99.78 0.28345 re f 403.37 361.134 0.22678 64.12 re f 403.597 361.134 49.096 0.28345 re f 452.693 361.134 0.28345 64.12 re f 452.976 361.134 46.715 0.28345 re f 499.691 361.134 0.28345 64.12 re f 499.975 361.134 45.751 0.28345 re f 100.517 316.063 m 49.833 316.063 l 49.833 316.29 l 100.516 316.29 l 100.516 316.063 l f* 100.517 316.063 0.22676 45.071 re f 100.743 316.063 55.786 0.22675 re f 156.529 316.063 0.22678 45.071 re f 156.756 316.063 45.808 0.22675 re f 202.564 316.063 0.22678 45.071 re f 248.315 316.063 m 202.79 316.063 l 202.79 316.29 l 248.315 316.29 l 248.315 316.063 l f* 248.315 316.063 0.22676 45.071 re f 248.542 316.063 54.822 0.22675 re f 303.364 316.063 0.22675 45.071 re f 303.59 316.063 99.78 0.22675 re f 403.37 316.063 0.22678 45.071 re f 403.597 316.063 49.096 0.22675 re f 452.693 316.063 0.28345 45.071 re f 452.976 316.063 46.715 0.22675 re f 499.691 316.063 0.28345 45.071 re f 499.975 316.063 45.751 0.22675 re f 100.517 280.46 m 49.833 280.46 l 49.833 280.687 l 100.516 280.687 l 100.516 280.46 l f* 100.517 280.46 0.22676 35.603 re f 100.743 280.46 55.786 0.22675 re f 156.529 280.46 0.22678 35.603 re f 156.756 280.46 45.808 0.22675 re f 202.564 280.46 0.22678 35.603 re f 248.315 280.46 m 202.79 280.46 l 202.79 280.687 l 248.315 280.687 l 248.315 280.46 l f* 248.315 280.46 0.22676 35.603 re f 248.542 280.46 54.822 0.22675 re f 303.364 280.46 0.22675 35.603 re f 303.59 280.46 99.78 0.22675 re f 403.37 280.46 0.22678 35.603 re f 403.597 280.46 49.096 0.22675 re f 452.693 280.46 0.28345 35.603 re f 452.976 280.46 46.715 0.22675 re f 499.691 280.46 0.28345 35.603 re f 499.975 280.46 45.751 0.22675 re f 100.517 254.324 m 49.833 254.324 l 49.833 254.608 l 100.516 254.608 l 100.516 254.324 l f* 100.517 254.324 0.22676 26.135 re f 100.743 254.324 55.786 0.28346 re f 156.529 254.324 0.22678 26.135 re f 156.756 254.324 45.808 0.28346 re f 202.564 254.324 0.22678 26.135 re f 248.315 254.324 m 202.79 254.324 l 202.79 254.608 l 248.315 254.608 l 248.315 254.324 l f* 248.315 254.324 0.22676 26.135 re f 248.542 254.324 54.822 0.28346 re f 303.364 254.324 0.22675 26.135 re f 303.59 254.324 99.78 0.28346 re f 403.37 254.324 0.22678 26.135 re f 403.597 254.324 49.096 0.28346 re f 452.693 254.324 0.28345 26.135 re f 452.976 254.324 46.715 0.28346 re f 499.691 254.324 0.28345 26.135 re f 499.975 254.324 45.751 0.28346 re f 100.517 209.254 m 49.833 209.254 l 49.833 209.48 l 100.516 209.48 l 100.516 209.254 l f* 100.517 209.254 0.22676 45.071 re f 100.743 209.254 55.786 0.22676 re f 156.529 209.254 0.22678 45.071 re f 156.756 209.254 45.808 0.22676 re f 202.564 209.254 0.22678 45.071 re f 248.315 209.254 m 202.79 209.254 l 202.79 209.48 l 248.315 209.48 l 248.315 209.254 l f* 248.315 209.254 0.22676 45.071 re f 248.542 209.254 54.822 0.22676 re f 303.364 209.254 0.22675 45.071 re f 303.59 209.254 99.78 0.22676 re f 403.37 209.254 0.22678 45.071 re f 403.597 209.254 49.096 0.22676 re f 452.693 209.254 0.28345 45.071 re f 452.976 209.254 46.715 0.22676 re f 499.691 209.254 0.28345 45.071 re f 499.975 209.254 45.751 0.22676 re f 100.517 183.118 m 49.833 183.118 l 49.833 183.402 l 100.516 183.402 l 100.516 183.118 l f* 100.517 183.118 0.22676 26.135 re f 100.743 183.118 55.786 0.28346 re f 156.529 183.118 0.22678 26.135 re f 156.756 183.118 45.808 0.28346 re f 202.564 183.118 0.22678 26.135 re f 248.315 183.118 m 202.79 183.118 l 202.79 183.402 l 248.315 183.402 l 248.315 183.118 l f* 248.315 183.118 0.22676 26.135 re f 248.542 183.118 54.822 0.28346 re f 303.364 183.118 0.22675 26.135 re f 303.59 183.118 99.78 0.28346 re f 403.37 183.118 0.22678 26.135 re f 403.597 183.118 49.096 0.28346 re f 452.693 183.118 0.28345 26.135 re f 452.976 183.118 46.715 0.28346 re f 499.691 183.118 0.28345 26.135 re f 499.975 183.118 45.751 0.28346 re f 100.517 128.523 m 49.833 128.523 l 49.833 128.806 l 100.516 128.806 l 100.516 128.523 l f* 100.517 128.523 0.22676 54.595 re f 100.743 128.523 55.786 0.28348 re f 156.529 128.523 0.22678 54.595 re f 156.756 128.523 45.808 0.28348 re f 202.564 128.523 0.22678 54.595 re f 248.315 128.523 m 202.79 128.523 l 202.79 128.806 l 248.315 128.806 l 248.315 128.523 l f* 248.315 128.523 0.22676 54.595 re f 248.542 128.523 54.822 0.28348 re f 303.364 128.523 0.22675 54.595 re f 303.59 128.523 99.78 0.28348 re f 403.37 128.523 0.22678 54.595 re f 403.597 128.523 49.096 0.28348 re f 452.693 128.523 0.28345 54.595 re f 452.976 128.523 46.715 0.28348 re f 499.691 128.523 0.28345 54.595 re f 499.975 128.523 45.751 0.28348 re f 100.517 83.679 0.22676 44.844 re f 156.529 83.679 0.22678 44.844 re f 202.564 83.679 0.22678 44.844 re f 248.315 83.679 0.22676 44.844 re f 303.364 83.679 0.22675 44.844 re f 403.37 83.679 0.22678 44.844 re f 452.693 83.679 0.28345 44.844 re f 499.691 83.679 0.28345 44.844 re f BT /F5 1 Tf 6.9999 0 0 6.9999 49.6063 760.3652 Tm 0.49804 0.49804 0.49412 scn 0 Tc 0 Tw [(TABLE)-306.1(3)-796.8(Summary)-301.7(of)-303.6(therapeutic)-302.7(HPV)-301.2(vaccines)-298.5(evalsuated)-303.4(as)-301.7(monotherapy)-302.4(in)-302.3(clinical)-305.2(trials.)]TJ /F1 1 Tf 9 0 0 9 62.8724 738.255 Tm 1 1 1 scn (Name)Tj 0.8945 -1.1087 TD (of)Tj -1.3354 -1.1087 TD (Vaccine)Tj 5.8583 1.1087 TD [(Sponsor)-1772.6(Adjuvant)-1097.9(Antigens)-1097.4(Indications)-3697.8(Outcomes)]TJ 33.3606 0.5543 TD (Vaccine)Tj 0.4724 -1.1087 TD (Types)Tj 5.3291 0.5543 TD [(Phase)-2928.1(Ref.)]TJ /F8 1 Tf 6.9999 0 0 6.9999 59.5275 687.6849 Tm 0.15294 0.15294 0.15294 scn (pNGVL4a-)Tj 0.6074 -1.3526 TD (CRT/E7)Tj 6.1715 3.3854 TD [(Sidney)-301.3(Kimmel)]TJ -0.0405 -1.3526 TD (Comprehensive)Tj 0.2187 -1.3606 TD [(Cancer)-304.4(Center)]TJ 2.5431 -1.3526 TD (at)Tj -2.6241 -1.3607 TD [(Johns)-301.4(Hopkins)]TJ 9.2006 2.7132 TD [(N.)-306.5(A.)-4950.7(E7)]TJ 13.1773 1.3606 TD (HPV-16)Tj 0.1053 -1.3606 TD (Positive)Tj -0.0972 -1.3526 TD [(CIN)-304.9(2/3)]TJ 9.7433 2.0329 TD (Well-tolerated.)Tj -2.2516 -1.3526 TD [(Robust)-302(immune)-308(response.)]TJ 14.8295 0.6722 TD [(DNA)-5636.4(I)-5652.3(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (77)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.2833 -7.1191 TD (AMV002)Tj 7.9776 2.0329 TD (Jingang)Tj -0.3483 -1.3526 TD (Medicine)Tj -0.2916 -1.3607 TD (\(Australia\))Tj 0.6641 -1.3526 TD [(Pty)-297.9(Ltd)]TJ 7.6942 2.0329 TD [(N.)-306.5(A.)-4173.2(E6,)-304.2(E7)]TJ 13.6551 1.3607 TD (HPV-)Tj -0.8261 -1.3607 TD (associated)Tj 0.4697 -1.3607 TD (OPSCC)Tj 9.6623 3.3935 TD [(Well)-302.8(tolerated.)]TJ -1.5145 -1.3526 TD [(E6/E7)-301.2(Speci)]TJ /F9 1 Tf 4.7866 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(c)-296.7(cellular)]TJ -7.1677 -1.3607 TD [(responses)-306(were)-305.7(elicited)-302.5(in)-300.5(10)-305.5(of)]TJ 2.4216 -1.3526 TD [(12)-297.4(\(83.3%\))-302.6(subjects)]TJ 13.4851 2.0329 TD [(DNA)-5636.4(I)-5652.3(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (78)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.4696 -5.7666 TD (INO-3112)Tj 8.3826 0.6803 TD (Inovio)Tj -1.9681 -1.3526 TD (Pharmaceuticals)Tj 9.4679 0.6722 TD [(N.)-306.5(A.)-4173.2(E6,)-304.2(E7)-2822.3(Cervical)-298.6(cancer)]TJ 20.8634 1.3606 TD [(Antibody)-306(responses)-306(were)]TJ 0.6155 -1.3606 TD [(detected)-304.3(in)-308.6(up)-296.4(to)-299.5(60%)]TJ 2.2111 -1.3526 TD [(of)-302.4(patients.)]TJ 11.8166 1.3526 TD [(DNA)-5474.4(II)-5481.2(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (79)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.1375 -5.7585 TD (VB10.16)Tj 7.7833 1.3526 TD (Nykode)Tj -1.0205 -1.3526 TD (Therapeutics)Tj 2.0005 -1.3606 TD (AS)Tj 6.7871 1.3606 TD [(N.)-306.5(A.)-4173.2(E6,)-304.2(E7)-4393.5(CIN2/3)]TJ 20.6042 2.0329 TD [(Eliciting)-303.3(CD8)]TJ 5.2498 0 0 4.6661 354.6707 569.7637 Tm (+)Tj 6.9999 0 0 6.9999 359.7731 566.6456 Tm [(T)-301.2(cells)-296.4(and)]TJ -6.6332 -1.3606 TD [(robust)-301(immune)-299.9(responses)-306(to)]TJ 0.486 -1.3526 TD [(regress)-307.4(the)-298(lesion)-301.3(size)-301.5(and)]TJ 0.1134 -1.3607 TD [(grade)-299.6(in)-300.5(CIN2/3)-304.6(patients.)]TJ 14.7242 2.041 TD [(DNA)-5474.4(II)-5481.2(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (80)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.2833 -5.0863 TD [(GX-188E)-3899.2(Genexine)-4325.1(N.)-306.5(A.)-4173.2(E6,)-304.2(E7)-4393.5(CIN2/3)]TJ 35.7091 0.6722 TD [(Signicant)-301.9(HPV)-305.5(clearance)-308.1(and)]TJ 0.5507 -1.3526 TD [(histopathologic)-299.9(regression.)]TJ 14.9429 0.6803 TD [(DNA)-5474.4(II)-5481.2(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (81)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.5911 -4.414 TD (VGX-3100)Tj 8.5041 0.6803 TD (Inovio)Tj -1.9681 -1.3526 TD (Pharmaceuticals)Tj 9.4679 0.6722 TD [(N.)-306.5(A.)-4173.2(E6,)-304.2(E7)-5033.4(CIN)]TJ 19.5189 1.3607 TD [(Showed)-297.8(ef)]TJ /F9 1 Tf 4.1225 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-297.8(against)-303(CIN2/3)]TJ -4.0253 -1.3607 TD [(associated)-309(with)-303.4(HPV-16)-297.5(and)]TJ 3.9929 -1.3526 TD (HPV-18.)Tj 11.3631 1.3526 TD [(DNA)-5223.4(IIb)-5232.3(\()]TJ 0.85098 0.19216 0.2 scn 14.1249 0 TD (82)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -66.0403 -5.7585 TD [(ISA)-301.9(201)]TJ 8.5041 0.6803 TD (ISA)Tj -2.5188 -1.3607 TD (Pharmaceuticals)Tj 9.4679 0.6803 TD [(N.)-306.5(A.)-4950.7(E6)]TJ 12.1406 2.0329 TD [(HPV)-297.4(positive)]TJ 0.5264 -1.3526 TD [(Tumors)-308.7(or)]TJ 0.1134 -1.3607 TD (Malignant)Tj 0.575 -1.3607 TD (Lesions)Tj 9.6056 3.3935 TD [(Well)-302.8(tolerated.)]TJ -2.535 -1.3526 TD [(Robust)-302(HPV-16-speci)]TJ /F9 1 Tf 8.7633 0 TD ()Tj /F8 1 Tf 0.5345 0 TD 0.2967 Tc [(cT)296.7(-)]TJ -6.7223 -1.3607 TD 0 Tc [(cell)-304.1(immunity.)]TJ 12.0839 1.3607 TD [(Peptide)-5216.6(I)-5652.3(\()]TJ 0.85098 0.19216 0.2 scn 14.546 0 TD (83)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -65.9998 -7.7995 TD (PepCan)Tj 6.5846 2.0329 TD [(University)-302.6(of)]TJ 0.0486 -1.3607 TD [(Arkansas)-310(for)]TJ 0.98 -1.3526 TD (Medical)Tj -0.0567 -1.3607 TD (Sciences)Tj 7.2568 3.3935 TD (Candida)Tj 0.8585 -1.3526 TD (skin)Tj -1.4821 -1.3607 TD [(test)-300.6(reagent)]TJ 8.3421 1.3607 TD [(E6)-5179.1(CIN2/3)]TJ 12.9181 3.3935 TD [(Regression)-311.5(rate:)-295.9(50%)-300.6(\(50)-302.6(and)]TJ 4.2115 -1.3607 TD (100)Tj /F14 1 Tf 1.7413 0 TD (m)Tj /F8 1 Tf 0.5669 0 TD (g\).)Tj -6.941 -1.3607 TD [(A)-301.1(trend)-303(of)-302.4(lower)-295.7(doses)-306.3(\(50)-302.7(and)]TJ 0.7046 -1.3526 TD (100)Tj /F14 1 Tf 1.4335 0 TD (m)Tj /F8 1 Tf 0.575 0 TD [(g\))-300.5(being)-303.4(more)-305.4(ef)67.2(fective)]TJ -1.798 -1.3607 TD [(than)-302.9(the)-298(higher)-299.1(doses)-306.3(\(250)]TJ 2.9724 -1.3526 TD [(and)-300(500)]TJ /F14 1 Tf 3.2316 0 TD (m)Tj /F8 1 Tf 0.575 0 TD (g\).)Tj 7.7752 3.3935 TD [(Peptide)-5216.6(I)-5652.3(\()]TJ 0.85098 0.19216 0.2 scn 14.546 0 TD (84)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -65.5625 -7.1272 TD (MVA)Tj -1.0124 -1.3526 TD [(E2)-303.5(vaccine)]TJ 8.0505 2.7132 TD (National)Tj -0.8909 -1.3607 TD (Autonomous)Tj 0.5426 -1.3526 TD (University)Tj 0.0567 -1.3607 TD [(of)-302.4(Me)]TJ /F15 1 Tf 2.3568 0.0405 TD ()Tj /F8 1 Tf 0.0405 -0.0405 TD (xico)Tj 5.8314 2.041 TD [(N.)-306.5(A.)-4950.7(E2)-3753.7(HPV)-305.5(infection)]TJ 19.5756 2.0329 TD [(Histology)-303(complete)-304.3(elimination)]TJ 0.2754 -1.3607 TD [(of)-302.4(lesions:)-302.4(89.3%)-300.2(\(female\))-304.3(and)]TJ 3.4097 -1.3526 TD [(100%)-299.5(\(male\).)]TJ -2.8023 -1.3607 TD [(HPV)-297.4(DNA)-299.1(clearance:)-308.8(83%.)]TJ 13.7442 2.041 TD [(Viral)-300.3(vector)-3999.1(III)-5318.3(\()]TJ 0.85098 0.19216 0.2 scn 15.4289 0 TD (85)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -67.1499 -5.7666 TD (ADXS11)Tj /F12 1 Tf 3.4907 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(001)-2418.2(Advaxis.)-305.6(Inc)-3699.1(N.)-306.5(A.)-4950.7(E7)]TJ 25.4232 0.6803 TD (Recurrent)Tj -0.98 -1.3606 TD [(cervical)-303.7(cancer)]TJ 8.7552 2.0329 TD [(12-month)-302.7(survival:)-307.6(30.9%.)]TJ 0 -1.3526 TD [(18-month)-302.7(survival:)-307.6(23.6%.)]TJ 2.7213 -1.3607 TD [(ORR:)-301.5(17.4%.)]TJ 10.8447 1.3607 TD [(Viral)-300.3(vector)-4169.2(II)-5481.2(\()]TJ 0.85098 0.19216 0.2 scn 15.4289 0 TD (54)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -67.2066 -3.7337 TD (Tipapkinogen)Tj 0.8585 -1.3526 TD (Sovacivec)Tj 8.3826 1.3526 TD (Taiho)Tj -1.6603 -1.3526 TD [(Oncology,)-301.7(Inc)]TJ 9.0386 0.6803 TD [(N.)-306.5(A.)-4319(E6,E7)-4551.9(CIN2/3)]TJ 24.3136 0.6722 TD (CR:24%)Tj 0.0486 -1.3526 TD (PR:12%)Tj 9.8405 0.6803 TD [(Viral)-300.3(vector)-4169.2(II)-5481.2(\()]TJ 0.85098 0.19216 0.2 scn 15.4289 0 TD (86)Tj 6.9999 0 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[(BLS-M07)-3542.7(BioLeaders)-4129.4(N.)-298.4(A)-5063.4(E)0(7)-5179.1(CIN2/3)-3657.7(CIN)-296.8(3)-306.6(cured)-299.1(in)-300.5(75%)-300.6(patients.)]TJ 50.5791 0.6803 TD (Bacterial)Tj 0.5021 -1.3606 TD (vector)Tj 7.2325 0.6803 TD [(I/IIa)-4940(\()]TJ 0.85098 0.19216 0.2 scn 7.0462 0 TD (88)Tj 0.15294 0.15294 0.15294 scn 0.9557 0 TD (\))Tj -67.0608 -5.7666 TD (IGMKK16E7)Tj 7.9291 0.6803 TD (GLOVACC)Tj 0.9314 -1.3607 TD [(Co)-301.9(Ltd)]TJ 7.7266 0.6803 TD [(N.)-298.4(A)-5063.4(E)0(7)-5179.1(CIN2/3)]TJ 21.1468 2.7132 TD [(31.7%)-300.2(CR)-301.2(in)-300.5(high-dose)]TJ 2.7213 -1.3526 TD (recipients)Tj -2.8347 -1.3607 TD (E7)Tj /F12 1 Tf 1.0448 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (speci)Tj /F9 1 Tf 1.9762 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(c)-296.7(interferon-)]TJ /F14 1 Tf 5.0701 0 TD (g)Tj /F8 1 Tf -10.4722 -1.3607 TD [(producing)-307(cells)-296.4(increased)-307.6(with)]TJ -0.0648 -1.3526 TD [(level)-299.6(of)-302.4(response)-305.5(\(SD,)-299.2(PR,)-306.9(CR\))]TJ 15.1049 3.3935 TD 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[(candidate)-264.3(for)-256(vaccine)-262.3(antigens)-258.9(in)-257.3(immunotherapy)-260.8(of)-261(pre-cancerous)]TJ 0 -1.3858 TD [(cervical)-447.5(lesions)-442(\()]TJ 0.85098 0.19216 0.2 scn 6.948 0 TD (109)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-446.9(E1)-439.3(is)-446.9(continuously)-446.8(expressed)-448(in)-446.2(the)-445.5(basal)]TJ -8.3843 -1.3921 TD [(epithelial)-320.2(cells)-326(after)-319.1(HPV)-324.3(infection)-321.8(and)-322.5(plays)-320.6(an)-319.6(important)-321(role)-322(in)]TJ 0 -1.3858 TD [(v)-8.1(i)-10.9(r)-14(u)-9.1(s)-517.9(r)-14(ep)-15.2(l)-14.6(i)-10.9(ca)-16.3(t)-13(i)-10.9(on)-527.5(\()]TJ 0.85098 0.19216 0.2 scn 7.7669 0 TD 0.0123 Tc [(11)12.3(0)]TJ 0.15294 0.15294 0.15294 scn 1.4677 0 TD 0.0111 Tc [(\).)-507.9(E1)-505.2(is)-513.1(c)11.1(r)-8.9(ucial)-507.4(f)11.1(or)-513.1(c)11.1(a)-5.2(rc)11.1(i)-5.8(n)-2.2(ogenesis)-513.1(\()]TJ 0.85098 0.19216 0.2 scn 15.515 0 TD 0 Tc [(11)-18.4(1)]TJ 0.15294 0.15294 0.15294 scn 1.4677 0 TD 0.0098 Tc (\).)Tj -26.2173 -1.3921 TD 0 Tc [(However,)-474.4(E1)-477.1(might)-471.6(not)-477.5(be)-476.1(an)-470.8(ideal)-479.2(target)-473.7(for)-476.5(vaccine)-476.4(antigens)]TJ 0 -1.3858 TD 0.0397 Tc [(due)-539.6(to)-537.5(its)-541.2(u)-0.9(b)4.3(i)-2.7(quitinati)3.6(o)-2(n)-540.6(a)-2(nd)-536.4(ra)]TJ 14.9669 0 TD 0.0401 Tc [(pid)-536(d)-0.5(egra)4.7(datio)4.7(n)-540.2(attributes)]TJ -14.9669 -1.3921 TD 0 Tc (\()Tj 0.85098 0.19216 0.2 scn 0.3465 0 TD (112)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (113)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (\).)Tj -2.1795 -1.3858 TD [(The)-360.2(minor)-363.9(capsid)-368(protein)-366.3(L2)-363.2(is)-358.7(a)-363(promising)-368.2(candidate)-365.1(for)-363.1(an)]TJ -1.5559 -1.3921 TD [(HPV)-387.3(vaccine)-382(since)-390.4(the)-382.5(linear)-383.9(neutralizing)-387.7(epitopes)-387(on)-382.6(the)-388.8(L2)-382.1(N-)]TJ 0 -1.3858 TD [(terminus)-225.7(are)-225.5(well)-227.5(conserved)-231.7(across)-225.8(several)-224.1(HPV)-229.8(genotypes)-226.5(\()]TJ 0.85098 0.19216 0.2 scn 23.6913 0 TD (114)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-226.4(In)]TJ -25.1276 -1.3921 TD [(mouse)-228.9(models,)-233.4(HPV-16)-228(L2)-224.6(antigen-induced)-238.1(neutralizing)-230.2(antibodies)]TJ 0 -1.3858 TD 0.0114 Tc [(protect)4.7(ed)-514.3(against)-511.8(i)0.5(n)4.4(f)0(ectious)-512.8(HPV-16)11.4(/)-6.5(4)-0.9(5)-511.2(c)-0.9(hallenges)-512.8(\()]TJ 0.85098 0.19216 0.2 scn 22.5323 0 TD 0.0123 Tc (115)Tj 0.15294 0.15294 0.15294 scn 1.4677 0 TD 0 Tc (,)Tj 0.85098 0.19216 0.2 scn 0.7433 0 TD 0.0123 Tc [(11)12.3(6)]TJ 0.15294 0.15294 0.15294 scn 1.4677 0 TD 0.0098 Tc (\).)Tj -26.211 -1.3921 TD 0 Tc [(Howe)-9.2(ver,)-509.3(L2)-501.8(m)-6.9(ight)-508.8(be)-501.3(le)-8(ss)-500.3(immu)-8.6(n)-7(ogenic)-508.2(s)-7.7(ince)-508.7(it)-502.6(is)-509.9(unable)-510.8(to)]TJ 0 -1.3858 TD 0.0695 Tc [(fo)-3.7(rm)-567.3(VL)-4.2(Ps)-574.4(\()]TJ 0.85098 0.19216 0.2 scn 6.2362 0 TD 0.0753 Tc [(11)6.3(7)]TJ 0.15294 0.15294 0.15294 scn 1.6504 0 TD 0.07 Tc [(\).)-568.7(There)-5.3(f)1.9(ore,)-568.7(strategie)-5.3(s)-567.6(to)-570.2(en)-6.3(hance)-572.3(t)0.3(he)]TJ -7.8866 -1.3921 TD 0 Tc [(immunogenicity)-410.9(of)-412.1(L2)-407.3(protein)-410.4(have)-406.8(become)-410.8(attractive)-406.8(\()]TJ 0.85098 0.19216 0.2 scn 23.0677 0 TD (114)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.6299 0 TD (118)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn -26.5701 -1.3858 TD (119)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-251.6(Notably,)-249.5(peptide)-258.6(antigens)-252.6(\()]TJ 0.85098 0.19216 0.2 scn 11.5906 0 TD (120)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.4661 0 TD (121)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\))-249.1(and)-253.2(HSP70-based)-254.6(fusion)]TJ -16.3717 -1.3921 TD [(proteins)-399.1(are)-395.6(widely)-392.2(tested)-394.9(in)-395.8(both)-390.6(preclinical)-399.1(and)-398.1(clinical)-395.2(studies)]TJ 0 -1.3858 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3465 0 TD (122)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (123)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (\).)Tj /F1 1 Tf 11.9999 0 0 11.9999 49.6063 209.9339 Tm [(4.2)-299(Adjuvant)-305.9(optimization)]TJ /F8 1 Tf 9 0 0 9 63.6094 184.989 Tm 0.0107 Tc (Cervarix)Tj /F13 1 Tf 7.4999 0 0 7.4999 95.1874 188.9575 Tm 0 Tc ()Tj /F8 1 Tf 9 0 0 9 105.5055 184.989 Tm 0.0107 Tc [(and)-508.7(G)0.6(ardasil)]TJ /F13 1 Tf 7.4999 0 0 7.4999 154.7149 188.9575 Tm 0 Tc ()Tj /F8 1 Tf 9 0 0 9 165.033 184.989 Tm 0.0111 Tc [(we)11.1(r)-8.9(e)-511.5(formulated)-508.3(with)-509.9(A)11.1(S)-5.5(04)-511.5(and)]TJ -12.8252 -1.3921 TD 0.0224 Tc [(amorphous)-520.7(a)-0.4(lumi)5.2(num)-519.9(h)-0.9(ydroxyphos)]TJ 15.5717 0 TD 0.0215 Tc [(phate)-520(s)-5.1(ulfa)5(te,)-522.7(r)-5(esp)-6.5(e)2.9(ctivel)-5.7(y)]TJ -15.5717 -1.3858 TD 0 Tc (\()Tj 0.85098 0.19216 0.2 scn 0.378 0 TD 0.0312 Tc (124)Tj 0.15294 0.15294 0.15294 scn 1.5307 0 TD 0 Tc (,)Tj 0.85098 0.19216 0.2 scn 0.7811 0 TD 0.0312 Tc (125)Tj 0.15294 0.15294 0.15294 scn 1.5307 0 TD 0.0314 Tc [(\).)-531.7(A)-6(l)4.2(um-based)-532.1(adjuvants)-530.6(c)-6.1(ould)-532.1(induce)-529(Th2-)-5.1(biased)]TJ -4.2205 -1.3921 TD 0.0331 Tc [(imm)-5.3(u)-1.2(ne)-539.9(resp)-7.5(on)-5.4(ses)-535.2(\()]TJ 0.85098 0.19216 0.2 scn 9.1843 0 TD 0.0375 Tc [(12)6.3(6)]TJ 0.15294 0.15294 0.15294 scn 1.5433 0 TD 0.0362 Tc [(\).)-533.2(The)-530.5(i)0.1(mm)4.1(unos)3.3(ti)6.4(mulant)-531.1(MPL,)-533.2(on)4(e)]TJ -10.7276 -1.3858 TD 0.0319 Tc [(compon)6(ent)-529.1(o)2.8(f)-527.5(t)0(he)-528.5(AS0)7(4)-528.5(adjuvant)6.3(,)-531.2(a)2.8(ctivates)-530.1(in)6(nat)6.3(e)-528.5(im)6.1(mun)6(e)]TJ 0 -1.3921 TD 0.0119 Tc [(responses)-512.3(t)-1.1(hrough)-509.1(Toll-like)-510.7(r)4.2(eceptor)-512.3(4)-510.7(\(TLR4\))-514.4(and)-507.5(i)1(nduces)-512.3(a)]TJ 0 -1.3858 TD 0.0096 Tc [(mixe)9.6(d)-515.8(T)0(h1)9.6(/)-8.3(T)0(h2)-506.7(immune)-506.7(response)-513(\()]TJ 0.85098 0.19216 0.2 scn 15.5213 0 TD 0 Tc [(12)-18.4(7)]TJ 0.15294 0.15294 0.15294 scn 1.4614 0 TD 0.0159 Tc [(\))6.1(.)-503.1(P)4.7(a)15.9(rt)9.2(i)5(c)15.9(ip)6.8(a)5.7(n)8.9(ts)-502(r)8.2(e)15.9(ce)15.9(iv)7.8(ed)]TJ -16.9827 -1.3921 TD 0 Tc (Cervarix)Tj /F13 1 Tf 7.4999 0 0 7.4999 80.4472 101.4803 Tm ()Tj /F8 1 Tf 9 0 0 9 89.0645 97.4551 Tm [(displayed)-336.9(stronger)-338.2(humoral)-334(and)-335.1(CD4)]TJ 6.7499 0 0 5.9992 225.6377 101.4803 Tm (+)Tj 9 0 0 9 232.4976 97.4551 Tm [(T)-330.9(cell)-337.3(responses)]TJ -20.3213 -1.3858 TD [(against)-262.4(HPV-16)-265.8(and)-259.5(18)-257.7(than)-261.4(patients)-265.8(received)-267.8(Gardasil)]TJ /F13 1 Tf 7.4999 0 0 7.4999 247.4645 88.9512 Tm ()Tj /F8 1 Tf 9 0 0 9 255.4582 84.9827 Tm (\()Tj 0.85098 0.19216 0.2 scn 0.3402 0 TD (125)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.4787 0 TD (128)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn -26.5701 -1.3921 TD (129)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD [(\).)-503.6(Meanwh)-9(ile,)-506.4(distincti)-12.8(ve)-505.5(immune)-506.7(pro)]TJ /F9 1 Tf 16.0882 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(les)-507(induc)-10.7(ed)-500.2(by)-503.4(HPV)]TJ 10.3055 76.2709 TD [(vaccines)-339.2(formulated)-343.9(with)-340.2(an)-344.8(Alum-based)-343.1(adjuvant,)-342.2(or)-339.1(AS04,)-339.8(have)]TJ 0 -1.3858 TD [(been)-300.2(reported)-301.9(\()]TJ 0.85098 0.19216 0.2 scn 6.2236 0 TD (129)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (130)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (\).)Tj -8.063 -1.3921 TD [(Adjuvants)-424.9(may)-415.8(af)60.3(fect)-420.7(the)-414(strength)-425.9(and)-417(durability)-418.7(of)-418.4(antigen-)]TJ -1.5496 -1.3858 TD (speci)Tj /F9 1 Tf 1.978 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(c)-308.4(immune)-311.4(responses.)-310.9(Exploratory)-314.3(studies)-309.1(of)-311.4(novel)-304.3(adjuvants)]TJ -2.5071 -1.3921 TD [(used)-220.9(alone)-224.5(or)-219.5(in)-219.5(combination)-222.3(have)-224.1(highlighted)-226.3(their)-218.3(potential)-226.3(use)-224.4(in)]TJ 0 -1.3858 TD [(HPV)-469.2(vaccines)-477.8(\()]TJ 0.85098 0.19216 0.2 scn 6.6142 0 TD [(Table)-472.7(4)]TJ 0.15294 0.15294 0.15294 scn 3.1685 0 TD [(\).)-472.1(Bacterial-derived)-483.6(components,)-476.3(such)-474.5(as)]TJ -9.7827 -1.3921 TD 0.0308 Tc [(Beclin-1)-529.6(\()]TJ 0.85098 0.19216 0.2 scn 4.4472 0 TD 0.0312 Tc (105)Tj 0.15294 0.15294 0.15294 scn 1.5307 0 TD 0.0297 Tc [(\),)-533.4(AS04)-530.7(\()-5.3(N)0.2(LX)-5.6(+Alu)-4.6(m\))-534.4(\()]TJ 0.85098 0.19216 0.2 scn 10.5764 0 TD 0.0312 Tc (25)Tj 0.15294 0.15294 0.15294 scn 1.0205 0 TD 0.0316 Tc [(\),)-531.5(CI)5.5(A06B)-531.9(\(nontoxic)]TJ -17.5748 -1.3858 TD 0 Tc [(derivative)-493.2(of)-494(lipopolysaccharide)-499(\(CIA05\))-497.3(+)-492.6(Alum\))-493.5(\()]TJ 0.85098 0.19216 0.2 scn 21.915 0 TD (100)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD [(\),)-491(rough)]TJ -23.3575 -1.3921 TD [(LPS)-240.6(\(R-LPS\))-243.2(\()]TJ 0.85098 0.19216 0.2 scn 5.6 0 TD (98)Tj 0.15294 0.15294 0.15294 scn 0.9638 0 TD [(\),)-239(and)-240.6(bacterial)-246.3(enzymatic)-244.3(combinatorial)-247.7(chemistry)]TJ -6.5638 -1.3858 TD [(\(BECC\)-derived)-408.8(TLR4)-414(agonists/Alum)-412.9(\()]TJ 0.85098 0.19216 0.2 scn 16.0819 0 TD (70)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD [(\),)-409.1(are)-408.2(widely)-411.1(utilized)-413.5(in)]TJ -17.0394 -1.3921 TD [(exploratory)-302.8(studies.)]TJ 1.5496 -1.3858 TD -0.0168 Tc [(I)-16.8(n)-490.8(addition)-16.8(,)-492.4(n)1.4(ovel)-510.1(molecules)-509.5(w)5.1(it)]TJ 13.3417 0 TD [(h)-506.3(d)-0.7(istinc)-4(tive)-507.9(contr)-16.8(i)15.1(butions)-503.2(t)-16.8(o)]TJ -14.8913 -1.3921 TD -0.0216 Tc [(i)5.3(m)-3.3(munogenicity)-470.7(are)-474.9(b)-0.3(eing)-470.7(evalsu)-5.5(a)5.9(ted)-478(i)-1(n)-469.6(p)-5.5(reclini)5.3(c)-2.5(al)-470.8(studies)-470.2(of)-473.9(HPV)]TJ 0 -1.3858 TD 0 Tc [(v)-8.1(a)0(c)-16.3(c)-12.3(in)-17.9(es)-13.7(,)-544.2(s)-7.7(u)-9.1(c)-12.3(h)-539.9(a)-10.2(s)-536.8(C)-11.7(p)-9.1(G)-539.2(o)-10.2(l)-8.3(ig)-19(od)-13.1(e)-12.3(o)-10.2(xy)-18.9(n)-7(u)-9.1(c)-12.3(l)-8.3(eo)-16.3(t)-6.7(i)-10.9(d)-9.1(e)-541.5(\()-9.8(C)0(p)-14.5(G)-10.1(\))-545.2(\()]TJ 0.85098 0.19216 0.2 scn 23.0173 0 TD (71)Tj 0.15294 0.15294 0.15294 scn 0.9701 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.7622 0 TD [(10)-18.4(4)]TJ 0.15294 0.15294 0.15294 scn 1.4614 0 TD 0.0098 Tc (\),)Tj -26.211 -1.3921 TD -0.0213 Tc [(po)6.3(lyinosini)5.6(c)-2.2(-polycytidylic)-298.2(acid)-301.3(\(Po)6.3(l)-4.4(y)-300.3(I)3(:C\))-301.9(\()]TJ 0.85098 0.19216 0.2 scn 16.2646 0 TD -0.0192 Tc [(10)6.3(4)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0217 Tc (\),)Tj /F14 1 Tf 0.8189 0 TD 0 Tc (a)Tj /F8 1 Tf 0.6047 0 TD -0.0216 Tc [(-)4.8(G)-0.2(alactosylceramide)]TJ -19.0614 -1.3858 TD 0 Tc (\()Tj /F14 1 Tf 0.3213 0 TD (a)Tj /F8 1 Tf 0.5984 0 TD -0.0201 Tc [(-GalCe)5.3(r\))-288.1(\()]TJ 0.85098 0.19216 0.2 scn 3.9685 0 TD -0.0255 Tc (73)Tj 0.15294 0.15294 0.15294 scn 0.9134 0 TD -0.0227 Tc [(\),)-289.7(very)-289.1(s)-5.2(m)1.9(all)-295.5(s)1.1(ize)-293.3(p)-0.3(rot)-4.2(e)2.8(olipos)-5.2(om)-4.4(es)-294.9(\(VSSP\))-290.7(\()]TJ 0.85098 0.19216 0.2 scn 16.5732 0 TD -0.0255 Tc (75)Tj 0.15294 0.15294 0.15294 scn 0.9134 0 TD -0.0223 Tc [(\),)-289.3(poly)-295(di)]TJ -23.2882 -1.3921 TD 0 Tc [(\(ca)11.8(rboxyl)14(atoeth)12.4(ylphe)14.4(noxy\))-512(phos)12.6(phazene)-508.8(\(PC)11.4(EP\))-517.2(\()]TJ 0.85098 0.19216 0.2 scn 20.7307 0 TD (99)Tj 0.15294 0.15294 0.15294 scn 0.9512 0 TD [(\),)-516.2(c-di-A)14.6(MP)]TJ -21.6819 -1.3858 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3213 0 TD -0.0255 Tc [(10)-6.3(1)]TJ 0.15294 0.15294 0.15294 scn 1.3669 0 TD -0.0216 Tc [(\),)-465(S-540956)-462.3(\(a)-466.5(Cp)-5.5(G)-460.1(O)-0.7(ligonucleoti)5.3(de\))-466(\()]TJ 0.85098 0.19216 0.2 scn 15.5843 0 TD -0.0192 Tc (72)Tj 0.15294 0.15294 0.15294 scn 0.9134 0 TD -0.0217 Tc [(\),)-465.1(th)5.4(e)-468.7(m)2.9(etal)-464.6(ions)-470.3(like)]TJ -18.1858 -1.3921 TD -0.0183 Tc [(ma)-18.3(n)8.5(g)-18.3(a)7.4(n)-18.3(e)6.4(s)-18.3(e)-498.1(\()-18.3(M)6.6(n)-18.3(4)]TJ 6.7499 0 0 5.9992 367.9369 537.9023 Tm 0 Tc (+)Tj 9 0 0 9 371.6786 533.8771 Tm [(\))15.4(-)13.8(do)24.7(p)16.1(e)12.8(d)-494.2(s)0(i)25.6(l)0(i)25(c)12.9(a)-495.3(n)0(a)26.8(n)0(o)26.8(p)16.1(ar)26.2(ti)26.6(c)12.8(l)0(e)23.5(s)-492.7(\()15.4(M)0(n)27.6(4)]TJ 6.7499 0 0 5.9992 496.5731 537.9023 Tm (+)Tj 9 0 0 9 500.3148 533.8771 Tm [(-)13.8(S)0(N)22.8(P)14(s\))-483.6(\()]TJ 0.85098 0.19216 0.2 scn 3.5906 0 TD -0.0129 Tc (74)Tj 0.15294 0.15294 0.15294 scn 0.9323 0 TD -0.0154 Tc (\),)Tj -26.2362 -1.3858 TD 0 Tc [(plan)-9.5(t)-523.2(e)0(x)-10.5(tract)-12.1(s)-524.2(lik)-8.9(e)-528.9(Bai)-534.2(Hua)-531.8(She)-531.4(She)-531.4(Cao)-529.8(\(BH)-8.5(SS)-8.9(C\))-531.7(\()]TJ 0.85098 0.19216 0.2 scn 22.7465 0 TD (102)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD [(\),)-528.8(and)]TJ -24.189 -1.3921 TD [(mR)-10.2(NA)-10.2(-e)-11.1(n)-7(c)0(o)-10(d)0(e)-8.9(d)-538.3(ST)-7.8(I)-7.2(N)0(G)]TJ 6.7499 0 0 5.9992 395.0361 512.9007 Tm [(V1)-16.7(55)-16.3(M)]TJ 9 0 0 9 420.4345 508.8755 Tm (\()Tj 0.85098 0.19216 0.2 scn 0.3465 0 TD [(10)-12.1(6)]TJ 0.15294 0.15294 0.15294 scn 1.4551 0 TD [(\),)-541.4(Ca)-9.4(n)-7(did)-16.5(a)-533.1(s)-7.7(kin)-543.1(t)-6.7(est)-543.2(rea)-17.6(ge)-7.9(n)-7(t)]TJ -14.6394 -1.3858 TD -0.0202 Tc [(\(E)6.4(xtract)-297.7(o)7.4(f)-302.4(C)5.9(a)1.1(ndida)-295(a)1(lb)7.4(icans\))-294.5(\()]TJ 0.85098 0.19216 0.2 scn 11.8551 0 TD -0.0192 Tc [(10)6.3(3)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0217 Tc (\).)Tj -11.6787 -1.3921 TD 0.0198 Tc [(A)-5(l)5.2(thoug)5.4(h)-520.1(many)-523.8(novel)-517.6(a)3.3(djuvan)]TJ 13.3795 0 TD 0.0184 Tc [(ts)-518.4(have)-523.1(de)-6.5(monstrated)-519.9(their)]TJ -14.9291 -1.3858 TD 0.0275 Tc [(uniqu)-6.8(e)-532.9(ef)]TJ /F9 1 Tf 4.1827 0 TD 0 Tc ()Tj /F8 1 Tf 0.5606 0 TD 0.0311 Tc [(c)6.2(a)-4.3(c)6.2(y)-531.4(in)-530.3(m)5.3(o)2(dulat)5.5(i)1.3(ng)-531.4(im)5.3(mune)-529.3(re)6.2(sponses)-524.6(i)1.3(n)-530.3(m)-1(ouse)]TJ -4.7433 -1.3921 TD 0 Tc [(models,)-340.4(only)-336(a)-337.8(few)-342(have)-337.5(been)-344.3(licensed)-338.2(for)-344.2(use)-337.8(in)-339.1(humans)-341.4(to)-338.2(date,)]TJ 0 -1.3858 TD [(primarily)-432.4(due)-440(to)-432.6(safety)-440.6(concerns.)-438.1(Therefore,)-436.9(novel)-436.6(HPV)-437.7(vaccine)]TJ 0 -1.3921 TD 0.5811 Tc [(a)539.4(d)540.5(j)541.3(u)540.5(v)535.2(a)539.4(n)542.6(t)536.6(sr)535.7(e)543.6(q)536.8(u)540.5(i)538.7(r)541.9(e)-4.5(f)538.2(u)540.5(r)535.7(t)542.9(h)538.9(e)537.3(rs)535.6(a)539.4(f)538.2(e)543.6(t)536.6(ya)539.4(n)536.3(d)-1.3(e)537.3(f)]TJ /F9 1 Tf 18.0095 0 TD 0 Tc ()Tj /F8 1 Tf 0.5669 0 TD 0.0427 Tc [(cacy)-538.7(validati)6.6(on)-543.9(in)]TJ -18.5764 -1.3858 TD 0 Tc [(clinical)-300.7(trials.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 304.8944 371.3952 Tm [(4.3)-299(Combination)-305.3(with)-302.8(immune)-302.4(checkpoint)]TJ 0 -1.0441 TD [(blockade)-304.7(therapy)]TJ /F8 1 Tf 9 0 0 9 318.8409 333.9212 Tm [(HPVs)-369.7(employ)-370(multiple)-367.6(strategies)-367.4(to)-363.3(evade)-367.2(the)-369.9(host)]TJ /F12 1 Tf 20.9197 0 TD ()Tj /F8 1 Tf 0.2205 0 TD [(s)-366.7(immune)]TJ -22.6898 -1.3921 TD 0.0356 Tc [(res)-3.6(p)-5(on)-2.9(se,)-540.1(i)-0.5(n)-2.9(c)-1.9(l)-4.2(u)1.3(d)-5(i)-0.5(n)-2.9(g)-539.5(in)-2.9(t)-2.6(e)-1.9(rf)-7.3(eren)-2.9(ce)-537.4(w)-5.5(i)-0.5(t)-2.6(h)-535.8(an)-2.9(t)-2.6(i)-0.5(g)-4(e)-1.9(n)-538.4(p)-5(res)-3.5(e)-1.9(n)-2.9(t)-2.6(at)-2.6(ion)-2.9(,)]TJ 0 -1.3858 TD 0.0168 Tc [(downregulation)-519.4(of)-517.4(antigen)-519.4(p)1.4(ro)-6(duction,)-521.1(i)-0.4(nhibitio)-6(n)-513.1(o)0.3(f)-517.4(a)-6(ntiviral)]TJ 0 -1.3921 TD 0 Tc [(mol)-12.8(ec)-12.1(ul)-11.1(es,)-520.1(s)-7.7(u)0(p)-12(p)0(r)-10.5(ess)-15(io)-8.5(n)-511(o)0(f)-519.2(t)0(y)-8.5(p)0(e)-512.8(1)-510(T)-513.6(h)0(e)-10.5(l)0(p)-11.1(e)0(r)-517.6(\(Th)-17.5(1\))-513.4(ce)-12.1(ll)-514.2(im)-11.5(m)-6.9(u)0(n)-9.9(e)]TJ 0 -1.3858 TD [(responses,)-468.4(and)-461(promotion)-469.5(of)-462.5(regulatory)-466.4(T)-463.2(cell)-463.3(\(Treg\))-466.7(responses)]TJ 0 -1.3921 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3402 0 TD (84)Tj 0.15294 0.15294 0.15294 scn 0.9575 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.4724 0 TD (131)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD [(\).)-257.9(Therapeutic)-255.9(HPV)-261.3(vaccine-evoked)-258.8(antigen-speci)]TJ /F9 1 Tf 19.7984 0 TD ()Tj /F8 1 Tf 0.5354 0 TD [(c)-251.7(T)-255.3(cells)]TJ -23.5465 -1.3858 TD [(are)-269.6(the)-269.1(key)-274.8(to)-268.9(tumor)-273.6(cell)-274.3(elimination)-271.4(and)-272.1(rely)-275.8(primarily)-275(on)-269.2(the)-269.1(loss)]TJ 0 -1.3921 TD [(of)-254.7(inhibitory)-263.3(signals)-255.1(in)-263.6(the)-256.5(tumor)-261(microenvironment)-263.9(\(TME\).)-260.2(Thus,)]TJ 0 -1.3858 TD 0.0286 Tc [(the)-525.5(c)-2.6(ombination)-526.5(of)-530.8(therapeutic)-525.5(H)1.2(PV)-527.9(vaccines)-527.1(and)-528.6(i)-1.2(mmune)]TJ 0 -1.3921 TD 0.0829 Tc [(checkpoint)-578.9(i)-3.6(nhibitors)-579.9(m)0.4(ay)-580.4(sh)]TJ 14.6835 0 TD 0.0824 Tc [(ow)-582.3(syne)-5.5(rgistic)-585.1(e)0.8(f)64.7(f)-4.6(ects)-580.4(i)-4.1(n)]TJ -14.6835 -1.3858 TD 0 Tc [(tumor)-298.8(regression.)]TJ 1.5496 -1.3921 TD [(Preclinical)-489.4(studies)-479.2(have)-482.4(demonstrated)-490.2(that)-475.2(therapeutic)-486(HPV)]TJ -1.5496 -1.3858 TD [(vaccines,)-486.6(such)-487.1(as)-490.3(adenovirus)-489.2(delivery)-492.6(vectors)-487.1(carrying)-487.8(modi)]TJ /F9 1 Tf 25.3165 0 TD ()Tj /F8 1 Tf 0.5291 0 TD (ed)Tj -25.8457 -1.3921 TD [(HPV-16)-284.7(E6)-281.8(and)-291(E7)-281.8(genes,)-289.3(HPV-16)-284.7(E7)-288.1(long)-285.6(peptide)-290.1(with)-283.5(DCs,)-288.1(and)]TJ 0 -1.3858 TD 0.0483 Tc [(the)-543.6(L)-0.2(m-)5.4(LLO)-548.1(f)5.4(u)-4.9(sed-E)5.6(6)-549.9(vaccine)-543.6(\()0.7(Lm-LLO-)5.4(E)-0.7(6\),)-546.3(s)2.9(igni)]TJ /F9 1 Tf 23.5654 0 TD 0 Tc ()Tj /F8 1 Tf 0.5732 0 TD 0.0488 Tc [(cant)4.3(ly)]TJ -24.1386 -1.3921 TD 0 Tc [(promoted)-506.9(tumor)-500.4(regressi)-11.3(on)-502.3(and)-498.8(surviva)-11.4(l)-499.6(rate)-503(in)-502.9(tumor-bear)-10.5(ing)]TJ 0 -1.3858 TD [(m)-6.9(o)0(u)-13.1(s)-7.7(e)-516.3(m)-6.9(o)-10.2(d)0(e)-15.2(l)0(s)-519.9(w)-9.6(he)-10.5(n)-517.3(u)-9.1(s)-7.7(e)0(d)-525.4(w)0(i)-14.2(t)-6.7(h)-514.7(a)-514.2(p)-9.1(r)-7.7(og)-12.1(r)-7.7(a)-10.2(m)-6.9(m)-6.9(e)0(d)-525.4(d)-9.1(ea)-16.3(t)-6.7(h)0(-)-15.8(l)0(i)-12.8(g)-8.1(an)-17.3(d)-513.1(1)]TJ 0 -1.3921 TD [(\(P)-14.7(D)-8(-)0(L)-15.8(1)0(\))-519.7(i)-10.9(n)-7(h)-10.7(ib)-14.8(it)-17.5(or)-521.8(\()]TJ 0.85098 0.19216 0.2 scn 8.3528 0 TD [(13)-12.1(2)]TJ /F12 1 Tf 0.15294 0.15294 0.15294 scn 1.4614 0 TD ()Tj /F8 1 Tf 0.85098 0.19216 0.2 scn 0.5165 0 TD [(13)-12.1(4)]TJ 0.15294 0.15294 0.15294 scn 1.4614 0 TD [(\).)-522.5(T)-9.6(h)0(e)-520.7(c)-12.3(li)-12.8(n)-7(i)-10.9(ca)-16.3(l)-512.2(t)-6.7(r)-14(i)0(a)-14.8(l)-8.3(s)-511.6(o)-10.2(f)-515.3(t)-6.7(h)-10.7(e)0(r)-13.7(a)-10.2(p)-9.1(e)0(u)-15.2(t)-6.7(i)-10.9(c)]TJ -11.7921 -1.3858 TD 0.0155 Tc [(HP)4.3(V)-515.8(v)1.1(acci)4.6(nes)-515(c)3.2(ombi)4.6(ned)-516.5(w)5.9(ith)-518.1(I)2(CB)-516.5(therapeu)6.4(ti)4.6(c)-513.4(m)-4(o)5.3(d)0.1(alities)-515(a)-1(re)]TJ 0 -1.3921 TD 0 Tc [(mainly)-498.7(in)-496.6(Phase)-505.7(I/II.)-495.6(Preliminary)-504.3(data)-502.4(show)-498.1(good)-497.6(ef)]TJ /F9 1 Tf 22.526 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-502.9(and)]TJ -23.0551 -1.3858 TD [(safety,)-291.9(and)-291(further)-292.3(veri)]TJ /F9 1 Tf 9.1465 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cation)-290.4(in)-295.1(later)-290.8(clinical)-288.1(trials)-290.7(is)-295.7(needed.)-291.6(The)]TJ -9.6756 -1.3921 TD [(current)-302.2(status)-300(of)-305.1(combination)-297.9(trials)-303.3(is)-302(listed)-300.6(in)]TJ 0.85098 0.19216 0.2 scn 18.9984 0 TD [(Table)-302.7(5)]TJ 0.15294 0.15294 0.15294 scn 2.9984 0 TD (.)Tj ET 0.49804 0.49804 0.49804 scn 49.833 702.538 240.605 47.622 re f 0.63529 0.63529 0.63529 scn 290.438 484.101 0.28348 281.424 re f 49.606 484.101 0.22676 281.424 re f 49.833 484.101 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[(reduced)-310.7(HPV)]TJ 5.2498 0 0 4.6661 213.7889 547.9369 Tm (+)Tj 6.9999 0 0 6.9999 175.5779 535.2944 Tm [(tumor)-304.4(growth.)]TJ 11.7923 5.4345 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (106)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -29.2946 -9.8404 TD (Chitosan)Tj 7.9857 0.6803 TD (DNA)Tj -0.3888 -1.3526 TD (vaccine)Tj 6.2525 2.7132 TD [(Strong)-307(induction)-303.1(of)-302.4(E7-)]TJ -0.8585 -1.3606 TD (speci)Tj /F9 1 Tf 1.9843 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(c)-304.8(CD8)]TJ 5.2498 0 0 4.6661 192.1322 512.3337 Tm (+)Tj 6.9999 0 0 6.9999 197.2346 509.2157 Tm [(T)-301.2(cells,)-305.2(IFN-)]TJ /F14 1 Tf 5.0782 0 TD (g)Tj /F8 1 Tf -10.5775 -1.3526 TD [(responses,)-306.6(and)-300(therapeutic)]TJ 1.9438 -1.3607 TD [(antitumor)-303.2(ef)59.1(fects)]TJ 12.254 2.0329 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (107)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj /F1 1 Tf 0.49804 0.49804 0.49412 scn -31.5704 42.3585 TD [(Wang)-305.1(et)-300.8(al.)]TJ 57.1394 0 TD (10.3389/fimmu.2024.1362770)Tj -57.1394 -109.3302 TD [(Frontiers)-304.6(in)]TJ 0.85098 0.19216 0.2 scn 5.5074 0 TD (Immunology)Tj 58.8564 0 TD (frontiersin.org)Tj 0.15294 0.15294 0.15294 scn -29.5213 0 TD (08)Tj ET endstream endobj 231 0 obj<> endobj 232 0 obj<> endobj 233 0 obj<> endobj 234 0 obj<> endobj 235 0 obj<> endobj 236 0 obj<> endobj 237 0 obj<> endobj 238 0 obj<> endobj 239 0 obj<> endobj 240 0 obj<> endobj 241 0 obj<> endobj 242 0 obj<> endobj 243 0 obj<> endobj 244 0 obj<> endobj 245 0 obj<> endobj 246 0 obj<> endobj 247 0 obj<> endobj 248 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 249 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 250 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 251 0 obj<>/Font<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 252 0 obj<>stream /GS1 gs BT /F1 1 Tf 11.9999 0 0 11.9999 49.6063 328.252 Tm /Cs6 cs 0.15294 0.15294 0.15294 scn 0 Tc 0 Tw [(4.4)-299.5(HPV)-302.9(L1)-300.2(VLP)-301.4(vaccine)-303(as)]TJ 0 -1.0394 TD [(adjuvant)-307(therapy)]TJ /F8 1 Tf 9 0 0 9 63.6094 290.7779 Tm [(L1)-268.7(VL)18.6(Ps)18.9(-)13.8(b)0(a)23.6(s)0(e)17.8(d)-286.3(H)16.7(P)0(V)-278(v)0(a)25.7(c)0(c)19.4(i)0(n)19.9(e)12.9(s)-284.8(h)0(a)23.1(v)0(e)-272.5(b)0(e)21.5(e)0(n)-277.6(a)15(pp)19.5(ro)19.9(ve)23.6(d)-286.3(p)0(r)21(i)14.3(ma)20.7(ri)19.3(ly)-268.4(fo)16.2(r)]TJ -1.5559 -1.3921 TD [(th)20.4(e)-295.8(p)0(r)21(e)0(v)17.3(e)12.9(nt)24.1(io)16.7(n)-296.8(o)0(f)-286.2(c)0(e)19.4(r)0(v)22(i)0(c)20.9(a)0(l)-289.4(c)12.9(an)20.5(c)12.8(e)0(r)-290.9(i)0(n)-288.8(p)0(o)24.7(p)0(u)19.5(l)0(a)19.3(t)0(i)20.3(o)15(ns)-291.8(w)15.6(i)0(t)20.3(h)0(o)23.1(u)0(t)-293(p)0(r)21(e)12.8(e)12.8(x)0(i)16.2(s)0(t)23.5(i)14.3(ng)]TJ 0 -1.3858 TD [(HP)24.4(V)-260.5(i)14.3(nf)19.4(ec)19.4(ti)20.3(o)15(n)0(.)-248.9(S)14.5(tu)15.7(d)16.1(i)0(e)20.9(s)-259.6(h)14.5(a)0(v)19.4(e)-258(su)21(gg)21.5(e)12.9(s)0(t)17.2(e)12.9(d)-254.8(a)0(n)-244(i)0(n)19.9(d)0(i)17.8(s)0(p)21(e)12.8(ns)23.1(ab)17.3(le)-241.1(ro)19.9(le)-247.4(o)15(f)-257(HP)18.1(V)]TJ 0 -1.3921 TD [(L1)-426.2(VL)18.6(P)-433.3(v)0(a)19.4(c)12.8(ci)20.9(ne)18.4(s)-436(a)0(s)-427.3(a)0(d)18.4(j)0(u)20.4(v)0(a)25.7(n)0(t)-429.4(t)0(h)20.4(e)12.9(ra)19.9(py)-426.7(af)22.5(te)18.8(r)-436(s)0(u)21(r)0(g)22(i)0(c)20.9(a)0(l)-428(t)0(r)23.5(e)12.8(at)20.9(me)18.6(nt)-423.1(fo)16.2(r)]TJ 0 -1.3858 TD 0.0173 Tc [(pati)6.4(ent)4.3(s)-525.8(suf)62.6(f)5.9(ering)-526.3(f)-0.4(rom)-525(H)2.5(PV-rel)]TJ 13.9906 0 TD 0.0164 Tc [(ated)-528.2(clinical)-527.3(diseases)-526.7(such)-529.8(as)]TJ -13.9906 -1.3921 TD 0.0136 Tc [(recurrent)-522.2(respir)5.9(atory)-523.7(p)-1.8(apill)5.3(o)-2.9(matosis)-523.2(\()3.8(RRP\))-519(\()]TJ 0.85098 0.19216 0.2 scn 19.263 0 TD 0.0123 Tc (140)Tj 0.15294 0.15294 0.15294 scn 1.474 0 TD 0.0132 Tc [(\))-525.7(a)3(nd)-525.1(cervical)]TJ -20.737 -1.3858 TD 0.0167 Tc [(intraepi)5.8(thelial)-527(n)3.4(eoplasia)-529(\(C)5(IN)6.1(\))-528.5(\()]TJ 0.85098 0.19216 0.2 scn 14.085 0 TD 0.0186 Tc [(14)6.3(1)]TJ 0.15294 0.15294 0.15294 scn 1.4866 0 TD 0.0163 Tc [(\).)-521.6(The)-525.2(d)-5.4(a)6.1(t)-3(a)-523.1(r)-4(eported)-522(t)-3(ha)6.1(t)]TJ -15.5717 -1.3921 TD 0 Tc [(su)14.7(rg)15.7(ic)14.6(al)-490.9(in)13.6(te)12.5(rv)15.7(en)12.1(ti)20.3(on)-489.7(an)14.2(d)-500.5(H)0(P)18.1(V)-499.9(va)13.1(cc)13.1(in)19.9(at)14.6(ion)-481.7(com)20.9(bin)22.3(at)14.6(ion)-481.7(th)14.1(er)11.5(ap)12.1(y)]TJ 0 -1.3858 TD [(ca)15.2(n)-498.4(e)0(f)70.8(f)0(e)14.1(c)0(t)12.5(i)0(v)12.5(e)0(l)17.2(y)-499.5(re)11.5(du)13.2(ce)-490.8(th)14.1(e)-497.4(r)0(e)11.5(c)0(u)16.3(rre)16.4(nc)12.1(e)-497.4(a)0(n)14.2(d)-500.5(se)11.5(ve)17.3(ri)13(ty)-493.5(of)-487.7(re)11.5(sp)14.7(ir)13(ato)17(ry)]TJ 0 -1.3921 TD [(papillom)15.2(atosis)-500.5(\()]TJ 0.85098 0.19216 0.2 scn 6.6016 0 TD (142)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-503.6(Likewis)11.2(e,)-506.2(anothe)12.1(r)-511.6(study)-500.5(has)-507.4(repo)11(rted)-508.2(that)]TJ -8.0378 -1.3858 TD 0.0159 Tc [(HPV)-528(v)1.5(accination)-526.6(signi)]TJ /F9 1 Tf 9.8205 0 TD 0 Tc ()Tj /F8 1 Tf 0.548 0 TD 0.0151 Tc [(cantly)-528.5(pr)-5.2(olongs)-528(the)-526.4(i)-2.1(nterv)-5.6(a)-1.4(ls)-521.7(between)]TJ -10.3685 -1.3921 TD 0 Tc [(su)21(rg)22(ic)20.9(al)-390.2(pr)21(oc)21.5(ed)16.3(ur)21(e)12.8(s)-404.5(a)15(n)0(d)-394.1(r)0(e)17.8(d)0(u)19.5(c)12.9(e)12.9(s)-404.5(th)20.4(e)-402.9(n)0(u)21.6(m)0(b)20.7(e)12.8(r)-404.5(o)0(f)-393.2(p)0(r)21(o)15(ce)19.4(du)19.5(re)24.1(s)-404.5(i)0(n)-395.8(t)0(h)26.7(e)]TJ 0 -1.3858 TD [(ma)20.7(jo)25.6(ri)19.3(ty)-462(of)-462.5(RR)18.6(P)-471.1(p)0(a)18.4(t)0(i)20.3(e)12.8(nt)24.1(s)-473.8(\()]TJ 0.85098 0.19216 0.2 scn 11.1496 0 TD -0.0129 Tc [(14)-12.9(3)]TJ 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\).)-465.8(M)15.7(o)0(s)19.9(t)-472.8(CI)18.9(N)14.6(s)-473.8(ar)19.9(e)-472.2(c)0(a)15.2(u)16.1(se)17.8(d)-475.3(b)15(y)-474.3(H)0(P)18.1(V)]TJ -12.5543 -1.3921 TD [(in)19.9(f)13.8(e)0(c)19.4(t)0(i)20.3(o)15(n)-347.2(\()]TJ 0.85098 0.19216 0.2 scn 4.1197 0 TD -0.0129 Tc [(14)-12.9(4)]TJ 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\))-343.6(a)0(n)20.5(d)-343(mi)20(gh)18.9(t)-340.5(p)0(r)21(o)0(g)19.4(r)0(e)24.1(s)0(s)-336.6(t)0(o)-331.9(c)0(e)19.4(r)0(v)22(i)0(c)20.9(a)0(l)-333.5(c)0(a)21.5(n)0(c)18.4(e)12.8(r)-347.8(\()]TJ 0.85098 0.19216 0.2 scn 16.4346 0 TD -0.0129 Tc (145)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD -0.0145 Tc [(\).)-363.4(CI)-14.5(N)-347.2(1)]TJ -23.3638 -1.3858 TD 0 Tc [(ra)19.9(re)24.1(ly)-274.7(pr)21(og)19.4(re)24.1(ss)22.5(es)-278.3(to)-268.9(ma)20.7(li)18.7(gn)22.6(an)20.5(c)12.8(y)-285.3(wi)23.6(th)-275.7(a)-281.1(h)0(i)22.5(g)0(h)-277.1(p)0(o)24.7(t)0(e)18.8(n)0(t)24.1(i)0(a)23(l)-285.4(fo)22.5(r)-284.8(r)0(e)17.8(g)0(r)22(e)12.8(ss)22.5(io)16.7(n.)]TJ 0 -1.3921 TD [(In)23.6(st)17.2(e)12.9(a)0(d)18.4(,)-481.2(CI)18.9(N)-483(2)-484.8(an)20.5(d)-487.9(3)12.9(,)-487.5(a)0(s)-471.4(t)0(h)20.4(e)-484.8(hi)22.5(gh)18.9(-)13.8(g)0(r)22(a)0(d)18.4(e)-484.8(le)23.5(si)19.3(on)20.5(s,)-476.3(b)15(e)0(c)19.4(o)0(m)20.7(e)-484.8(hi)22.5(gh)18.9(ly)]TJ 0 -1.3858 TD [(c)12.9(a)0(n)20.5(c)0(e)19.4(r)0(o)19.9(u)0(s)-356.9(w)0(i)17.3(t)0(h)-357.5(a)-369.3(lo)19.3(w)15.6(e)0(r)-360.2(p)0(o)18.4(t)0(e)18.8(n)0(t)24.1(i)14.3(al)-365(f)13.8(o)0(r)-358(r)0(e)17.8(g)0(r)22(e)12.9(ss)16.2(i)14.3(o)0(n)-363.7(\()]TJ 0.85098 0.19216 0.2 scn 19.6787 0 TD [(14)19.4(6)]TJ 0.15294 0.15294 0.15294 scn 1.4047 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5921 0 TD -0.0129 Tc (147)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\))15.4(.)-374.1(St)20.4(ud)19.5(i)14.3(e)0(s)]TJ -23.0803 -1.3921 TD [(ha)23.1(ve)-228.4(re)24.1(po)18.4(rt)23.5(e)12.9(d)-235.9(th)20.4(at)-224.8(va)19.4(c)12.8(c)12.9(in)19.9(at)20.9(io)23(n)-240.1(w)15.6(it)20.3(h)-237.5(t)0(h)26.7(e)-239.1(q)12.4(u)0(a)18.4(d)0(r)21(i)14.3(va)19.4(le)23.5(nt)-227.9(HP)24.4(V)-235.3(v)0(a)19.4(c)12.8(ci)20.9(ne)-227.2(in)]TJ 28.3654 28.0252 TD 0.0181 Tc [(patients)-531.3(after)-531.3(l)3.5(oop)-532.8(electrosurg)]TJ 13.1906 0 TD 0.0178 Tc [(ical)-532.2(excision)-531(pro)-5(c)5.5(edure)-530(\()-4.6(LEEP\))]TJ -13.1906 -1.3858 TD 0 Tc [(tr)23.5(e)12.8(a)0(t)20.9(m)0(e)18.6(n)0(t)-423.1(s)0(i)25.6(g)0(n)16.3(i)]TJ /F9 1 Tf 6.0661 0 TD ()Tj /F8 1 Tf 0.5228 0 TD [(c)12.8(a)0(n)20.5(t)0(l)22.9(y)-436.5(pr)21(e)12.8(v)0(e)17.3(n)0(t)24.1(s)-436(th)20.4(e)-434.4(r)0(e)24.1(c)0(u)16.3(r)0(r)22.5(e)12.8(nc)18.4(e)-434.4(o)0(f)-424.7(C)13.5(IN)20(2)]TJ /F12 1 Tf 16.1386 0 TD ()Tj /F8 1 Tf 0.5039 0 TD 0.4344 Tc [(3r)434.4(e)458.5(l)434.4(a)453.7(t)434.4(e)459.5(d)]TJ -23.2315 -1.3921 TD 0 Tc [(to)-281.5(va)25.7(cc)19.4(in)19.9(e)-289.5(H)0(P)18.1(V)-292(ty)23(pe)16.3(s)-291.1(c)12.8(om)20.7(pa)18.4(re)24.1(d)-292.6(w)0(i)17.3(t)0(h)-282(n)0(o)20.5(n)0(-)25.7(H)0(P)18.1(V)0(-)24.2(v)0(a)19.4(c)12.9(ci)20.9(na)20.5(te)18.8(d)-292.6(p)0(a)18.4(t)0(i)26.6(e)0(n)18.4(t)0(s)]TJ 0 -1.3858 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3276 0 TD [(14)19.4(8)]TJ 0.15294 0.15294 0.15294 scn 1.4047 0 TD [(\).)-283.1(Th)23.7(es)17.8(e)-289.5(d)0(a)18.4(t)0(a)-275.2(d)0(e)16.3(m)0(o)27(n)0(s)16.8(t)0(r)23.5(a)0(t)20.9(e)-289.5(th)20.4(at)-281.5(HP)24.4(V)-292(v)0(a)19.4(c)12.9(c)12.8(i)0(n)19.9(a)0(t)20.9(i)0(o)23(n)-290.5(pl)20.4(ay)19.4(s)-291.1(a)-287.4(cr)17.8(i)14.3(t)0(i)20.3(c)0(a)21.5(l)]TJ -1.7323 -1.3921 TD [(ro)26.2(le)-234.8(as)-232.1(ad)18.4(ju)20.4(va)25.7(nt)-234.2(th)20.4(er)17.8(a)14.9(p)0(y)-237.7(i)14.3(n)-246.4(H)0(P)18.1(V)0(-)24.2(r)0(e)17.8(l)0(a)25.6(t)0(e)18.8(d)-242.2(di)17.8(so)26.2(rd)21(er)17.8(s)-247(o)15(th)20.4(e)12.8(r)-247(th)20.4(a)14.9(n)-246.4(ca)21.5(nc)18.4(e)12.8(r)0(.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 304.8944 239.7543 Tm [(4.5)-299(Exploration)-303.1(in)-301.9(formulation)-306.2(strategy,)]TJ 0 -1.0441 TD [(dosing)-299.5(regimens,)-303.1(and)-301.9(expansion)-309.7(of)]TJ 0 -1.0394 TD [(vaccine)-303(recipients)]TJ 10.5001 0 0 10.5001 304.8944 190.2047 Tm [(4.5.1)-295.5(Alternative)-307.9(strategies)-301.3(for)-303.2(HPV)]TJ 0 -1.1392 TD [(vaccine)-298.9(formulation)]TJ /F8 1 Tf 9 0 0 9 318.8409 165.7134 Tm [(Hi)18.4(gh)-251.9(co)21.5(st)17.2(,)-267(c)12.9(ol)25.6(d)-267.4(c)0(h)21(a)0(i)16.7(n)-265.3(st)23.5(or)19.9(a)15(g)0(e)-259.9(a)15(nd)-255.5(de)16.3(li)25(ve)17.3(ry)22(,)-260.7(a)0(n)20.5(d)-267.4(re)17.8(q)12.4(u)0(i)24.1(r)0(e)17.8(m)0(e)18.6(n)0(t)24.1(s)-265.9(fo)22.5(r)]TJ -1.5496 -1.3858 TD [(tr)23.5(a)14.9(i)0(n)19.9(e)0(d)-393.1(v)0(a)19.4(c)12.9(c)12.8(i)0(n)19.9(a)0(t)20.9(o)0(r)19.9(s)-398.2(li)18.7(mi)26.3(t)-403.5(v)0(a)19.4(c)12.9(c)12.9(i)0(n)19.9(a)0(t)20.9(i)0(o)23(n)-403.9(c)12.8(o)0(v)19.4(e)12.8(ra)19.9(ge)23.6(,)-405.6(w)15.6(hi)22.5(ch)-394.7(pr)21(o)15(m)0(p)21.8(t)0(s)-392.3(t)0(h)20.4(e)]TJ 0 -1.3921 TD 0.0345 Tc [(dev)-5.1(e)3.2(lopment)-545.4(o)-0.9(f)-543.8(n)-4(ano-)-550.1(o)5.4(r)-546.4(micr)]TJ 14.0535 0 TD 0.035 Tc [(o-)4.7(p)-5.6(a)-0.4(rticulate)-544.3(v)1.7(accines)-545.9(\()]TJ 0.85098 0.19216 0.2 scn 10.589 0 TD 0.0375 Tc [(14)6.3(9)]TJ 0.15294 0.15294 0.15294 scn 1.5433 0 TD 0.035 Tc (\).)Tj -26.1858 -1.3858 TD 0 Tc [(N)14.6(a)0(n)20.5(o)0(t)20.9(e)12.8(ch)21(no)20.5(lo)19.3(gy)-337.5(h)14.5(a)0(s)-339.2(b)0(e)21.5(e)12.9(n)-353.5(e)12.9(xt)20.4(e)12.9(n)0(s)23.1(i)0(v)18.8(e)12.8(ly)-337.7(us)21(ed)-342.7(i)14.3(n)-347.2(va)19.4(cc)19.4(i)14.3(n)0(e)-340.6(d)0(e)22.6(v)0(e)17.3(l)0(o)25.6(p)0(m)21.8(e)0(n)18.4(t)]TJ 0 -1.3921 TD [(v)17.1(i)0(a)-222.7(t)0(h)20.4(e)-232.8(ut)22(il)18.7(i)14.3(t)0(y)-222.7(o)0(f)-223.2(a)0(d)18.4(v)0(a)19.4(n)0(c)24.7(e)0(d)-223(n)0(a)20.5(n)0(o)20.5(-)13.8(ba)17.3(se)24.1(d)-235.9(p)0(a)24.7(r)0(t)17.2(i)14.3(cl)17.2(e)12.9(s)-234.4(o)15(r)-234.4(ma)20.7(te)18.8(ri)25.6(al)19.3(s)-234.4(d)0(e)22.6(s)0(i)19.3(g)0(n)22.6(e)12.8(d)]TJ 0 -1.3858 TD [(f)13.8(o)0(r)-345.4(a)0(n)20.5(t)0(i)20.3(g)0(e)23.6(n)-359.8(de)22.6(li)25(ve)17.3(ry)-343.4(or)-345.4(as)-345.5(ad)18.4(ju)20.4(va)25.7(nt)17.8(s)-354.1(t)0(o)-344.5(e)0(n)18.4(h)14.5(an)20.5(ce)-346(im)20(mu)21.8(ne)-346.9(re)17.8(sp)21(o)15(n)0(s)16.8(e)12.8(s)]TJ 0 -1.3921 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3339 0 TD (150)Tj 0.15294 0.15294 0.15294 scn 1.4236 0 TD [(\).)-497.3(Ar)11.6(chae)17.3(oso)16(mes)-493(are)-490.1(com)14.6(mon)13.6(ly)-495.1(use)15(d)-506.8(i)0(n)-496.6(can)14.5(ce)13.1(r)-505.3(v)0(a)13.1(cci)14.8(nes)-493.2(as)]TJ -1.7575 -1.3858 TD [(d)16.1(e)0(l)17.2(i)14.3(ve)17.3(ry)-286.7(to)20.9(ol)19.3(s.)-287.3(HP)18.1(V)-298.3(D)0(N)19.2(A)-302(va)25.7(cc)19.4(in)19.9(e)12.9(s)-303.7(c)12.9(o)0(n)20.5(t)0(a)20.9(i)0(n)19.9(i)14.3(ng)-292.3(th)20.4(e)-302.1(t)0(r)23.5(u)0(n)21.6(c)12.9(at)20.9(ed)-292.3(L1)21(,)-298.5(E)0(6)20.5(,)]TJ ET 0.49804 0.49804 0.49804 scn 49.833 732.416 435.855 17.688 re f 485.688 750.104 m 545.726 750.104 l 545.726 732.416 l 485.688 732.416 l f* 0.63529 0.63529 0.63529 scn 49.606 750.104 496.346 0.28351 re f 545.726 371.622 0.22681 378.482 re f 49.606 371.622 0.22676 378.482 re f 49.833 371.622 495.893 0.28348 re f 92.013 732.416 m 49.833 732.416 l 49.833 732.699 l 92.013 732.699 l 92.013 732.416 l f* 92.013 732.416 0.22678 17.688 re f 92.239 732.416 63.496 0.28351 re f 155.735 732.416 0.28346 17.688 re f 156.019 732.416 55.276 0.28351 re f 211.294 732.416 0.28345 17.688 re f 271.332 732.416 m 211.578 732.416 l 211.578 732.699 l 271.332 732.699 l 271.332 732.416 l f* 271.332 732.416 0.22678 17.688 re f 271.559 732.416 90.198 0.28351 re f 361.757 732.416 0.22678 17.688 re f 361.984 732.416 123.704 0.28351 re f 485.688 732.416 0.28345 17.688 re f 485.972 732.416 59.754 0.28351 re f 92.013 687.345 m 49.833 687.345 l 49.833 687.572 l 92.013 687.572 l 92.013 687.345 l f* 92.013 687.345 0.22678 45.071 re f 92.239 687.345 63.496 0.22681 re f 155.735 687.345 0.28346 45.071 re f 156.019 687.345 55.276 0.22681 re f 211.294 687.345 0.28345 45.071 re f 271.332 687.345 m 211.578 687.345 l 211.578 687.572 l 271.332 687.572 l 271.332 687.345 l f* 271.332 687.345 0.22678 45.071 re f 271.559 687.345 90.198 0.22681 re f 361.757 687.345 0.22678 45.071 re f 361.984 687.345 123.704 0.22681 re f 485.688 687.345 0.28345 45.071 re f 485.972 687.345 59.754 0.22681 re f 92.013 623.225 m 49.833 623.225 l 49.833 623.509 l 92.013 623.509 l 92.013 623.225 l f* 92.013 623.225 0.22678 64.12 re f 92.239 623.225 63.496 0.28345 re f 155.735 623.225 0.28346 64.12 re f 156.019 623.225 55.276 0.28345 re f 211.294 623.225 0.28345 64.12 re f 271.332 623.225 m 211.578 623.225 l 211.578 623.509 l 271.332 623.509 l 271.332 623.225 l f* 271.332 623.225 0.22678 64.12 re f 271.559 623.225 90.198 0.28345 re f 361.757 623.225 0.22678 64.12 re f 361.984 623.225 123.704 0.28345 re f 485.688 623.225 0.28345 64.12 re f 485.972 623.225 59.754 0.28345 re f 92.013 587.622 m 49.833 587.622 l 49.833 587.905 l 92.013 587.905 l 92.013 587.622 l f* 92.013 587.622 0.22678 35.603 re f 92.239 587.622 63.496 0.28345 re f 155.735 587.622 0.28346 35.603 re f 156.019 587.622 55.276 0.28345 re f 211.294 587.622 0.28345 35.603 re f 271.332 587.622 m 211.578 587.622 l 211.578 587.905 l 271.332 587.905 l 271.332 587.622 l f* 271.332 587.622 0.22678 35.603 re f 271.559 587.622 90.198 0.28345 re f 361.757 587.622 0.22678 35.603 re f 361.984 587.622 123.704 0.28345 re f 485.688 587.622 0.28345 35.603 re f 485.972 587.622 59.754 0.28345 re f 92.013 533.027 m 49.833 533.027 l 49.833 533.31 l 92.013 533.31 l 92.013 533.027 l f* 92.013 533.027 m 92.013 587.622 l 92.239 587.622 l 92.239 533.027 l 92.013 533.027 l f* 92.239 533.027 63.496 0.28345 re f 155.735 533.027 m 155.735 587.622 l 156.019 587.622 l 156.019 533.027 l 155.735 533.027 l f* 156.019 533.027 55.276 0.28345 re f 211.294 533.027 m 211.294 587.622 l 211.578 587.622 l 211.578 533.027 l 211.294 533.027 l f* 271.332 533.027 m 211.578 533.027 l 211.578 533.31 l 271.332 533.31 l 271.332 533.027 l f* 271.332 533.027 m 271.332 587.622 l 271.559 587.622 l 271.559 533.027 l 271.332 533.027 l f* 271.559 533.027 90.198 0.28345 re f 361.757 533.027 m 361.757 587.622 l 361.984 587.622 l 361.984 533.027 l 361.757 533.027 l f* 361.984 533.027 123.704 0.28345 re f 485.688 533.027 m 485.688 587.622 l 485.971 587.622 l 485.971 533.027 l 485.688 533.027 l f* 485.972 533.027 59.754 0.28345 re f 92.013 449.915 m 49.833 449.915 l 49.833 450.198 l 92.013 450.198 l 92.013 449.915 l f* 92.013 449.915 0.22678 83.112 re f 92.239 449.915 63.496 0.28348 re f 155.735 449.915 0.28346 83.112 re f 156.019 449.915 55.276 0.28348 re f 211.294 449.915 0.28345 83.112 re f 271.332 449.915 m 211.578 449.915 l 211.578 450.198 l 271.332 450.198 l 271.332 449.915 l f* 271.332 449.915 0.22678 83.112 re f 271.559 449.915 90.198 0.28348 re f 361.757 449.915 0.22678 83.112 re f 361.984 449.915 123.704 0.28348 re f 485.688 449.915 0.28345 83.112 re f 485.972 449.915 59.754 0.28348 re f 92.013 423.836 m 49.833 423.836 l 49.833 424.063 l 92.013 424.063 l 92.013 423.836 l f* 92.013 423.836 0.22678 26.079 re f 92.239 423.836 63.496 0.22678 re f 155.735 423.836 0.28346 26.079 re f 156.019 423.836 55.276 0.22678 re f 211.294 423.836 0.28345 26.079 re f 271.332 423.836 m 211.578 423.836 l 211.578 424.063 l 271.332 424.063 l 271.332 423.836 l f* 271.332 423.836 0.22678 26.079 re f 271.559 423.836 90.198 0.22678 re f 361.757 423.836 0.22678 26.079 re f 361.984 423.836 123.704 0.22678 re f 485.688 423.836 0.28345 26.079 re f 485.972 423.836 59.754 0.22678 re f 92.013 397.757 m 49.833 397.757 l 49.833 397.984 l 92.013 397.984 l 92.013 397.757 l f* 92.013 397.757 0.22678 26.079 re f 92.239 397.757 63.496 0.22678 re f 155.735 397.757 0.28346 26.079 re f 156.019 397.757 55.276 0.22678 re f 211.294 397.757 0.28345 26.079 re f 271.332 397.757 m 211.578 397.757 l 211.578 397.984 l 271.332 397.984 l 271.332 397.757 l f* 271.332 397.757 0.22678 26.079 re f 271.559 397.757 90.198 0.22678 re f 361.757 397.757 0.22678 26.079 re f 361.984 397.757 123.704 0.22678 re f 485.688 397.757 0.28345 26.079 re f 485.972 397.757 59.754 0.22678 re f 92.013 371.905 0.22678 25.852 re f 155.735 371.905 0.28346 25.852 re f 211.294 371.905 0.28345 25.852 re f 271.332 371.905 0.22678 25.852 re f 361.757 371.905 0.22678 25.852 re f 485.688 371.905 0.28345 25.852 re f BT /F5 1 Tf 6.9999 0 0 6.9999 49.6063 760.3652 Tm 0.49804 0.49804 0.49412 scn [(TABLE)-306.1(5)-798.7(Clinical)-300.2(trials)-304.7(of)-303.6(therapeutic)-294.6(HPV)-301.2(vaccines)-306.6(in)-302.3(combination)-301.5(with)-297.8(ICB)-306.9(therapy.)]TJ /F1 1 Tf 9 0 0 9 54.6519 738.255 Tm 1 1 1 scn [(Vaccine)-1100.8(Combination)-1746.1(Sponsor)-2358.4(Phase)-301.3(\(N\))-2913.7(Safety)-305.5(Pro)]TJ /F10 1 Tf 30.5386 0 TD ()Tj /F1 1 Tf 0.5858 0 TD [(les)-6841.8(Ef)]TJ /F10 1 Tf 9.0079 0 TD ()Tj /F1 1 Tf 0.5858 0 TD [(cacy)-7535.8(Ref.)]TJ /F8 1 Tf 6.9999 0 0 6.9999 57.9401 707.6975 Tm 0.15294 0.15294 0.15294 scn [(GX-188E)-2554.7(Pembrolizumab)-2446.8(Genexine,)-308.7(Inc.)]TJ 25.8848 0.6803 TD (II)Tj -0.494 -1.3607 TD (\(36\))Tj 7.2811 2.7132 TD [(AEs:)-299.1(44%;)-301.3(Grade)-308.8(3)]TJ /F12 1 Tf 7.5889 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (4)Tj -6.2768 -1.3526 TD [(TRAE:)-309.9(11%.)]TJ -0.4293 -1.3607 TD [(No)-299.9(treatment-)]TJ -0.0081 -1.3526 TD [(related)-307.9(deaths.)]TJ 16.012 3.3854 TD [(ORR:)-301.5(42%.)]TJ 0.3483 -1.3526 TD [(CR:)-301.9(15%.)]TJ 0.0486 -1.3607 TD [(PR:)-298.8(27%.)]TJ 13.8819 1.3607 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (135)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.8864 -7.7995 TD [(ISA)-301.9(101)-3730.3(Nivolumab)]TJ 16.9677 0.6803 TD (ISA)Tj -2.5188 -1.3607 TD (Pharmaceuticals)Tj 11.193 1.3607 TD (II)Tj -0.494 -1.3607 TD (\(24\))Tj 7.1434 4.0739 TD [(Grades)-309.2(3)]TJ /F12 1 Tf 3.596 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(4)-298.5(toxicity:)-306.8(2)]TJ -4.4464 -1.3607 TD [(patients;)-300.9(Asymptomatic)]TJ -0.5588 -1.3526 TD [(grade)-299.6(3)-306.6(transaminase)-305.4(level)]TJ 1.385 -1.3607 TD [(elevation:)-300.3(1)-306.6(patient;)]TJ -0.9962 -1.3607 TD [(Grade)-300.7(4)-298.5(lipase)-304.3(elevation:)]TJ 3.0453 -1.3526 TD [(1)-298.5(patient.)]TJ 13.153 6.1068 TD [(mPFS:)-303.4(2.66)-296.9(months.)]TJ 0.1701 -1.3607 TD [(mOS:)-298.1(15.3)-305(months.)]TJ -0.2592 -1.3526 TD [(2-year)-302.5(OS)-299.5(rate:)-304(33%.)]TJ -2.4945 -1.3607 TD [(objective)-304.9(response:)-298.1(38%)-300.6(\(without)]TJ 2.0572 -1.3526 TD [(progression)-305.8(at)-297.7(3)-298.5(years\))]TJ 16.6518 2.7132 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (136)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.8945 -7.1191 TD [(TG4001)-3921.7(Avelumab)-4408(Transgene)]TJ 25.0668 0.6722 TD (Ib/II)Tj 0.0891 -1.3526 TD (\(34\))Tj 10.4884 0.6803 TD [(N.)-298.4(A.)]TJ 13.8414 1.3526 TD [(ORR:)-301.5(23.5%.)]TJ 0.5831 -1.3526 TD [(CR:)-302(2.9%.)]TJ -0.1863 -1.3607 TD [(PR:)-298.8(20.6%.)]TJ 14.2302 1.3607 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (137)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.765 -5.7666 TD (PRGN-)Tj 0.5345 -1.3606 TD (2009)Tj 7.1353 0.6803 TD (M7824)Tj 8.1882 1.3607 TD (National)Tj 0.324 -1.3607 TD (Cancer)Tj -1.6198 -1.3606 TD [(Institute)-304.7(\(NCI\))]TJ 10.6261 2.041 TD (I/II)Tj 0.081 -1.3606 TD (\(6\))Tj 7.6537 2.041 TD [(Grade)-308.8(1)]TJ /F12 1 Tf 3.2316 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (2)Tj /F9 1 Tf 0.7775 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (u-like)Tj -6.2363 -1.3607 TD [(syndrome;)-310.2(Injection)-304.4(site)]TJ -0.6641 -1.3606 TD [(reactions,)-304.6(fatigue,)-305.3(and)-300(rash.)]TJ 17.5022 4.0739 TD [(SD:)-302(2/3)-299.4(patients.)]TJ -4.0982 -1.3526 TD [(Increased)-307.5(T)-301.2(cells)-304.5(were)-297.6(detected)-304.3(in)-300.5(all)]TJ 0.2511 -1.3607 TD [(patients,)-309(with)-295.3(3/6)-299.4(\(50%\))-303.1(developing)]TJ 1.0205 -1.3606 TD [(HPV-16)-297.5(T)-301.2(cells)-304.5(and)-300(5/6)-299.4(\(83%\))]TJ 0.6074 -1.3525 TD [(developing)-301.9(HPV-18)-305.6(T)-293.1(cells.)]TJ 17.6237 2.7132 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (138)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -66.2671 -9.8323 TD [(PDS)-306.3(0101)]TJ 8.172 0.6722 TD (M9241)Tj -0.899 -1.3526 TD [(and)-300(M7824)]TJ 9.9457 2.0329 TD (PDS)Tj -1.9843 -1.3526 TD (Biotechnology)Tj 0.3888 -1.3606 TD (Corporation)Tj 10.3993 2.0329 TD (II)Tj -0.494 -1.3526 TD (\(14\))Tj 6.3416 0.6803 TD [(Manageable)-309.4(safety)-299.5(pro)]TJ /F9 1 Tf 9.0386 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (le.)Tj 3.1101 4.7461 TD [(Evidence)-306.8(of)-294.3(notable)-301.8(clinical)-304.4(activity)-306.2(for)]TJ -0.2754 -1.3606 TD [(patients)-308.3(with)-303.4(both)-297.1(checkpoint)-306.6(na飗e)-301.6(and)]TJ 2.0491 -1.3526 TD [(refractory)-299.7(HPV-16+)-308.6(advanced)]TJ 3.3773 -1.3607 TD (malignancies.)Tj -1.1096 -1.3526 TD [(ORR:)-301.5(10/14)-297.1(\(71%\).)]TJ -0.0486 -1.3607 TD [(CR:)-301.9(1\(anal)-299.2(cancer\).)]TJ -3.4178 -1.3526 TD [(PR:)-298.8(9)-298.5(\()0(3)-303.8(cervical,)-304.4(2)-298.5(vulvar/vaginal,)-311.8(2)]TJ 2.6322 -1.3607 TD [(anal,)-303.8(2)-298.5(oropharyngeal\).)]TJ 16.7247 4.7542 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (139)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -66.5263 -7.8076 TD [(MG1-E6E7)-2562.7(Atezolizumab)]TJ 16.2712 0.6803 TD (Turnstone)Tj -0.9881 -1.3526 TD [(Biologics,)-297.4(Corp)]TJ 11.1606 1.3526 TD (I)Tj -0.656 -1.3526 TD (\(75\))Tj 10.4884 0.6722 TD [(N.)-298.4(A.)-13155.1(N.)-298.4(A.)-9138(NCT03618953)]TJ -35.7415 -3.7256 TD [(ISA101b)-3410.8(Cemiplimab)]TJ 17.073 0.6803 TD (ISA)Tj -2.5188 -1.3607 TD (Pharmaceuticals)Tj 11.193 1.3607 TD (II)Tj 6.9999 0 0 6.9999 234.0283 403.8235 Tm (\(194\))Tj 10.7233 0.6803 TD [(N.)-298.4(A.)-13155.1(N.)-298.4(A.)-9138(NCT03669718)]TJ -36.0654 -3.7256 TD [(INO-3112)-3022(Durvalumab)]TJ 14.9996 0.6722 TD [(M.D.)-306.9(Anderson)]TJ 0.2268 -1.3526 TD [(Cancer)-304.4(Center)]TJ 10.8447 1.3526 TD (II)Tj -0.494 -1.3526 TD (\(77\))Tj 10.4884 0.6803 TD [(N.)-298.4(A.)-13155.1(N.)-298.4(A.)-9138(NCT03439085)]TJ 6.5001 0 0 6.5001 49.6063 363.1181 Tm [(AE,)-268.6(Adverse)-272.4(Event;)-267.8(TRAE,)-270.4(Adverse)-272.4(Event;)-267.8(ORR,)-265.8(Objective)-272.4(Response)-277(Rate;)-263.2(CR,)-273.8(Complete)-270.8(Response;)-268.3(PR,)-271.8(Partial)-266.2(Response;)-277(SD,)-268.3(Stable)-261(Disease;)-276(OS,)-267(Overall)-269.4(S)]TJ 62.0092 0 TD [(urvival;)-273.7(DCR,)-268.7(Disease)-267.2(Control)-271(Rate;)]TJ -62.0092 -1.3083 TD [(N.A.,)-301(not)-305.4(available.)]TJ /F1 1 Tf 6.9999 0 0 6.9999 49.6063 800.9573 Tm 0.49804 0.49804 0.49412 scn [(Wang)-305.1(et)-300.8(al.)]TJ 57.1394 0 TD (10.3389/fimmu.2024.1362770)Tj -57.1394 -109.3302 TD [(Frontiers)-304.6(in)]TJ 0.85098 0.19216 0.2 scn 5.5074 0 TD (Immunology)Tj 58.8564 0 TD (frontiersin.org)Tj 0.15294 0.15294 0.15294 scn -29.5213 0 TD (09)Tj ET endstream endobj 253 0 obj<> endobj 254 0 obj<> endobj 255 0 obj<> endobj 256 0 obj<> endobj 257 0 obj<> endobj 258 0 obj<> endobj 259 0 obj<> endobj 260 0 obj<> endobj 261 0 obj<> endobj 262 0 obj<> endobj 263 0 obj<> endobj 264 0 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[(c)12.9(y)0(t)16.7(o)15(ly)21.4(ti)20.3(c)-459.6(i)0(m)20(m)0(u)21.8(n)0(e)-454(r)0(e)24.1(s)0(p)21(o)0(n)20.5(s)0(e)17.8(s)-461.2(to)-451.5(e)12.9(l)0(i)18.7(m)0(i)20(n)0(a)26.8(t)0(e)-453.6(t)0(u)22(m)0(o)20.7(r)-461.2(ce)19.4(ll)21.3(s)-461.2(\()]TJ 0.85098 0.19216 0.2 scn 22.4252 0 TD -0.0129 Tc (151)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\).)-453.2(G)15.1(o)0(l)19.3(d)]TJ -23.8299 -1.3921 TD [(na)20.5(no)20.5(pa)24.7(rt)17.2(i)14.3(c)0(l)17.2(e)12.9(s)-417.1(c)12.9(an)-407.8(al)19.3(so)-402.1(be)-406.8(po)24.7(te)18.8(nt)24.1(ia)16.7(ll)21.3(y)-411.3(u)0(s)21(e)0(d)-412(i)14.3(n)-416.5(t)0(h)20.4(e)-415.5(HP)18.1(V)-411.7(v)0(a)19.4(c)0(c)19.4(i)0(n)19.9(e)-415.5(to)]TJ 0 -1.3858 TD [(st)23.5(re)17.8(ng)22.6(th)20.4(e)12.9(n)-214.9(c)12.9(y)0(t)23(o)0(t)20.9(o)15(xi)16.2(c)-207.6(i)0(m)20(m)0(u)21.8(n)0(e)-202(r)0(e)24.1(s)0(p)21(o)0(n)20.5(s)0(e)17.8(s)-209.2(by)-201(i)14.3(n)0(c)18.4(r)0(e)24.1(a)0(s)19.9(i)0(n)19.9(g)-209.7(ox)23.1(id)17.8(a)15(t)0(i)20.3(v)0(e)-203.2(s)0(t)23.5(r)0(e)17.8(s)0(s)]TJ 0 -1.3921 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3339 0 TD -0.0129 Tc (152)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\).)-201.2(C)13.5(h)0(i)22.5(t)0(o)20.9(s)0(a)19.9(n)-214.9(i)14.3(s)-215.5(a)15(l)0(s)21.9(o)-211.8(us)21(ed)-204.2(as)-200.6(a)-211.8(n)0(a)20.5(n)0(o)20.5(p)0(a)24.7(r)0(t)17.2(i)14.3(cl)17.2(e)-207.6(a)0(d)18.4(j)0(u)20.4(v)0(a)19.4(n)0(t)-196.4(d)0(u)19.5(e)-213.9(to)-199.6(it)20.3(s)-209.2(n)0(o)20.5(n)0(-)]TJ -1.7386 -1.3858 TD [(to)20.9(x)14.5(i)0(c)20.9(,)-418.2(h)14.5(i)0(g)18.8(h)14.5(ly)-400.7(bi)23(oc)21.5(om)20.7(pa)18.4(ti)20.3(b)15(l)0(e)17.2(,)-411.9(lo)25.6(w)-412.8(s)0(u)21(s)0(c)17.8(e)12.8(pt)22(ib)23(il)18.7(i)14.3(t)0(y)16.7(,)-411.9(a)15(n)0(d)-406.7(b)15(io)23(de)16.3(gr)22(ad)24.7(at)20.9(io)23(n)]TJ 0 -1.3921 TD [(pr)21(op)18.4(e)12.9(r)0(t)23.5(i)0(e)20.9(s)-303.7(\()]TJ 0.85098 0.19216 0.2 scn 4.5669 0 TD -0.0129 Tc (153)Tj 0.15294 0.15294 0.15294 scn 1.3984 0 TD 0 Tc [(\).)-295.7(C)13.5(h)0(i)22.5(t)0(o)20.9(s)0(a)19.9(n)0(-)19.4(b)15(as)19.9(e)12.9(d)-305.2(DN)25.5(A)-302(v)0(a)19.4(c)12.8(ci)20.9(ne)18.4(s)-297.4(e)0(x)21(p)0(r)21(e)0(s)17.8(s)0(i)19.3(n)0(g)-286(H)0(P)18.1(V)0(-)24.2(1)12.9(6)]TJ -5.9654 -1.3858 TD [(E7)-489.7(si)13(gn)16.3(i)]TJ /F9 1 Tf 3.3827 0 TD ()Tj /F8 1 Tf 0.5228 0 TD [(ca)15.2(ntl)22.1(y)-499.5(p)0(r)14.7(o)0(m)14.4(o)0(t)14.6(e)-497.4(T)-501(c)0(e)13.1(l)0(l)15(-)0(m)13.2(e)0(d)16.3(iat)16.3(ed)-487.6(im)13.7(mun)14.7(e)-497.4(r)0(e)17.8(spo)17.1(ns)16.8(e)-497.4(and)]TJ -3.9055 -1.3921 TD [(an)20.5(ti)20.3(bo)17.3(dy)-477.1(pr)14.7(od)18.4(uc)22.6(ti)20.3(on)-483.4(ag)19.4(ai)23(ns)16.8(t)-491.7(H)0(P)18.1(V)0(-)24.2(i)0(n)19.9(d)0(u)13.2(c)12.8(ed)-481.3(tu)15.7(mo)20.7(rs)-481.4(\()]TJ 0.85098 0.19216 0.2 scn 21.6189 0 TD -0.0129 Tc (154)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD 0 Tc [(\).)-478.4(He)16.9(nc)18.4(e)12.8(,)]TJ -23.0236 -1.3858 TD [(t)-6.7(h)0(e)-527(n)0(a)-11(n)0(o)-11(tec)-12.4(hn)-11.5(ol)-12.2(ogy)-13.9(-c)-11.1(rea)-11.3(t)-6.7(e)0(d)-525.4(H)-8.5(PV)-530(vac)-11.8(ci)-10.6(n)-7(e)-522.6(wo)-7.2(u)-9.1(l)0(d)-521.3(p)-9.1(r)-7.7(ovi)-10.3(d)-9.1(e)-522.6(mo)-10.8(re)]TJ 0 -1.3921 TD [(op)18.4(ti)14(on)14.2(s)-492.7(f)0(o)16.2(r)-492.7(th)14.1(e)-497.4(t)0(r)17.2(e)0(a)15.2(t)0(m)17.9(e)0(n)18.4(t)-498(of)-487.7(HP)18.1(V-)17.9(re)11.5(la)19.3(te)18.8(d)-500.5(d)0(i)17.8(s)0(e)17.8(a)0(s)13.6(e)0(s)17.8(.)-493.8(Add)19.9(it)14(io)16.7(na)20.5(ll)15(y,)]TJ 0 -1.3858 TD [(HP)24.4(V)-386.5(p)0(r)21(o)15(te)18.8(in)-370.6(an)20.5(ti)20.3(ge)23.6(ns)-373.7(c)12.9(a)0(n)-370(b)0(e)-375.3(f)13.8(or)19.9(mu)21.8(la)19.3(te)25.1(d)-380.8(i)0(n)19.9(t)0(o)-369.7(g)0(l)21.4(a)0(s)19.9(s)0(y)-368.5(m)0(i)20(c)12.8(ro)19.9(sp)21(he)21(re)17.8(s)]TJ 0 -1.3921 TD [(us)-10.5(ing)-523.7(spr)-11.8(ay-)-10.8(dri)-8.7(ed)-525.4(tech)-10.6(n)-7(ique)-13.7(s)-517.9(and)-524(t)-6.7(hen)-521.4(co)-10(ate)-10.3(d)-519.4(b)0(y)-522.3(ato)-8.2(mic)-521.4(l)-8.3(aye)-11.8(r)]TJ 0 -1.3858 TD [(de)22.6(po)18.4(si)19.3(ti)26.6(on)-294.4(\(A)22.1(LD)19.1(\))-305.8(w)15.6(it)20.3(h)-306.8(n)0(a)26.8(n)0(o)20.5(m)0(e)18.6(t)0(e)25.1(r)0(-)18.8(t)0(h)20.4(i)14.3(n)-309.4(p)16.1(ro)19.9(te)18.8(c)12.9(t)0(i)20.3(v)0(e)-291.3(l)0(a)19.3(y)0(e)23.6(r)0(s)-292.5(o)0(f)-292.5(a)0(l)19.3(u)0(m)21.8(i)0(n)19.9(a)]TJ 0 -1.3921 TD [(to)-501.9(impro)11.9(ve)-505.5(their)-501.8(ther)13(mostab)11.1(ility)-498.3(\()]TJ 0.85098 0.19216 0.2 scn 14.3748 0 TD (155)Tj 0.15294 0.15294 0.15294 scn 1.4299 0 TD [(\).)-503.6(Given)-495.7(the)-502.2(advant)11.6(age)-503.2(of)]TJ -15.8047 -1.3858 TD [(na)20.5(no)20.5(te)25.1(ch)21(no)20.5(lo)19.3(gy)-425.7(ut)22(il)18.7(i)14.3(z)0(a)21.5(t)0(i)20.3(o)0(n)-426.7(i)0(n)-433.6(H)16.7(PV)-429.2(va)19.4(c)12.8(c)0(i)20.9(n)0(e)-428.8(f)0(o)16.2(r)0(m)23.2(u)0(l)20.4(a)15(ti)20.3(on)20.5(,)-437.1(i)0(t)-433.3(w)15.6(ou)18.4(ld)]TJ 0 -1.3921 TD [(pr)21(ov)19.4(i)14.3(d)0(e)-456.1(m)0(o)20.7(r)0(e)-454.6(o)15(pt)22(io)23(ns)-455.6(fo)22.5(r)-467.5(p)0(a)24.7(t)0(i)20.3(e)0(n)18.4(t)0(s)-449(i)0(n)-458.8(p)16.1(re)17.8(ve)23.6(nt)17.8(i)14.3(o)0(n)-458.2(o)15(r)-467.5(t)0(r)23.5(e)12.9(at)20.9(me)18.6(nt)-454.6(o)15(f)]TJ 0 -1.3858 TD [(HP)24.4(V-)17.9(re)24.1(la)19.3(te)18.8(d)-317.8(d)0(i)17.8(s)0(e)24.1(a)0(s)19.9(e)0(s)17.8(.)-317.4(Ho)19.1(we)22.1(ve)23.6(r,)-312.5(th)20.4(e)-321(c)0(u)16.3(r)0(r)22.5(e)12.9(nt)-309.7(na)20.5(no)20.5(pa)18.4(rt)23.5(ic)20.9(le)-310.4(ag)19.4(e)12.9(n)0(t)17.8(s)-316.3(fo)16.2(r)]TJ 0 -1.3921 TD [(th)20.4(e)-314.7(H)0(P)24.4(V)-317.2(va)25.7(cc)19.4(in)19.9(e)-314.7(a)15(re)-303.5(st)17.2(i)14.3(l)0(l)-300(f)0(a)16.2(r)-310(aw)17.9(a)15(y)-316.8(f)13.8(o)0(r)-301.3(h)0(u)17.9(m)0(a)20.7(n)-315.7(u)16.1(s)0(e)17.8(,)-311.1(wi)17.3(th)-300.9(un)21.6(c)12.8(e)0(r)17.8(t)0(a)20.9(i)14.3(nt)17.8(y)]TJ 0 -1.3858 TD [(c)12.9(o)0(n)20.5(c)0(e)19.4(r)0(n)23.1(i)0(n)19.9(g)0(.)-369.7(F)0(u)19.5(r)0(t)23.5(h)0(e)21(r)-379.3(st)23.5(ud)19.5(ie)20.9(s)-379.3(r)0(e)24.1(g)0(a)19.4(r)0(d)21(i)0(n)19.9(g)-379.8(th)20.4(e)-377.7(s)0(a)19.9(f)13.8(e)12.8(t)0(y)16.7(,)-374.1(st)17.2(a)15(b)0(i)16.7(l)0(i)25(t)0(y)23(,)-380.4(po)18.4(te)25.1(nc)18.4(y,)]TJ 0 -1.3921 TD [(an)20.5(d)-286.3(r)0(a)19.9(p)0(i)17.8(d)-286.3(pr)21(od)18.4(uc)22.6(ti)20.3(on)-275.5(of)-279.9(HP)18.1(V)-285.7(a)0(r)19.9(e)-289.5(re)17.8(q)12.4(u)0(i)24.1(r)0(e)17.8(d)-286.3(to)-281.5(b)15(e)-289.5(ex)21(pl)20.4(or)19.9(e)12.9(d)0(.)]TJ 1.5559 -1.3858 TD -0.0211 Tc [(Oral)-413.6(admi)5.8(nistration)-412.4(of)-416.7(the)-411.4(H)1.9(PV)-413.9(vacci)5.8(ne)-411.4(is)-413(easy,)-414.1(w)0.8(ith)-409.8(f)-1(avorable)]TJ -1.5559 -1.3921 TD 0 Tc [(sa)26.2(fe)20.4(ty)-487.2(pr)27.3(o)]TJ /F9 1 Tf 4.0567 0 TD ()Tj /F8 1 Tf 0.5165 0 TD [(le)23.5(s)-499(a)0(n)20.5(d)-494.2(po)18.4(te)25.1(nt)24.1(i)14.3(a)0(l)-484.6(l)0(o)19.3(n)0(g)28.9(-)0(l)24.5(a)0(s)19.9(t)0(i)26.6(n)0(g)-487.6(p)0(r)21(o)15(te)25.1(ct)18.8(i)14.3(v)0(e)-486.6(e)12.8(f)70.5(f)13.8(e)12.8(c)12.9(ts)-486.8(in)-490.3(th)26.7(e)]TJ -4.5732 -1.3858 TD -0.0213 Tc [(intestine)-499.8(\()]TJ 0.85098 0.19216 0.2 scn 4.0315 0 TD -0.0192 Tc [(15)6.3(6)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0213 Tc [(\).)-502.5(Oral)-502(vaccination)-500.8(c)-2.2(o)6.3(u)-5.2(ld)-496.6(di)]TJ 11.3953 0 TD -0.0201 Tc [(m)4.5(i)0.5(n)4.4(i)0.5(sh)-497(vaccin)4.4(e)-498.6(h)0.7(esit)4.7(ancy)]TJ -16.8 -1.3921 TD -0.0203 Tc [(and)-363.3(boost)-360.8(v)3.1(accine)-360.2(co)7.3(vera)7.3(ge)-360.2(\()]TJ 0.85098 0.19216 0.2 scn 11.3449 0 TD -0.0255 Tc [(15)-6.3(7)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0218 Tc [(\).)-358.1(A)-367.9(c)3.6(linical)-363.9(s)2(tudy)-363.8(has)-363.3(r)-4.3(eported)-358.5(t)-3.3(hat)]TJ -12.7181 -1.3858 TD -0.0216 Tc [(an)-387.7(oral)-388.9(th)5.5(erapeuti)5.3(c)-393(v)1.8(accine)-393(has)-388.3(d)0.8(em)]TJ 14.3307 0 TD [(onstrated)-389.8(s)-4.1(af)4.8(ety)-388.8(a)-0.3(nd)-389.8(potency)-388.8(t)3.2(o)]TJ -14.3307 -1.3921 TD [(induce)-342.5(persistent)-336.8(immunity)-338.3(\()]TJ 0.85098 0.19216 0.2 scn 11.3071 0 TD -0.0255 Tc (90)Tj 0.15294 0.15294 0.15294 scn 0.9134 0 TD -0.0217 Tc [(\).)-339.1(The)-336.4(c)-2.6(ombinational)-332.3(ap)-5.6(plicati)5.2(o)-0.4(n)-343.7(o)5.9(f)-341.7(a)]TJ -12.2205 -1.3858 TD -0.0209 Tc [(nanotechno)6.7(lo)6.7(gy-b)6.7(ased)-219(DNA)-215.8(v)2.5(acci)6(ne)-215.9(and)-219(a)-220.1(VLP)-221.1(v)2.5(accine)-222.2(could)-219(p)1.5(otently)]TJ 0 -1.3921 TD 0 Tc [(st)17.2(im)20(ul)14.1(at)14.6(e)-503.7(b)0(o)17.3(t)0(h)-496.1(h)0(u)17.9(m)0(o)20.7(r)0(a)13.6(l)-505.9(an)20.5(d)-506.8(c)0(e)19.4(l)0(l)15(u)0(l)20.4(a)0(r)-496.6(i)0(m)13.7(m)0(u)15.5(n)0(i)19.9(t)0(y)16.7(,)-506.4(wh)17.5(ic)14.6(h)-502.1(h)0(a)16.8(s)-505.3(be)21.5(en)]TJ 0 -1.3858 TD -0.0215 Tc [(investigated)-301.5(for)-300(H)1.5(IV)-300.9(inf)4.9(e)-2.3(ction)-299.4(\()]TJ 0.85098 0.19216 0.2 scn 12.1449 0 TD -0.0192 Tc [(15)6.3(8)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0218 Tc [(\).)-301.4(Oral)]TJ /F9 1 Tf 2.8221 0 TD 0 Tc ()Tj /F8 1 Tf 0.5102 0 TD -0.0223 Tc [(lms)-300.8(h)-1.5(av)-5.2(e)-299.2(b)-1(een)-306.5(e)3.1(xtensively)]TJ -16.8504 -1.3921 TD -0.0212 Tc [(used)-219.3(in)-217.2(formulati)5.7(o)0.1(ns)-217.8(for)-217.8(t)3.6(he)-222.5(admini)5.7(stra)6.4(tion)-217.2(of)-221.5(many)-224.6(drugs)-224.1(\()]TJ 0.85098 0.19216 0.2 scn 22.5701 0 TD -0.0255 Tc [(15)-6.3(9)]TJ 0.15294 0.15294 0.15294 scn 1.3669 0 TD -0.0154 Tc [(\).)-213.1(F)7(i)5.2(l)7.8(m)9.2(-)]TJ -23.937 -1.3858 TD -0.0215 Tc [(based)-207(HPV)-212.7(v)1.9(accines)-205.5(w)0.4(ould)-207(be)-210.2(attracti)5.4(ve)-210.2(a)6(s)-211.8(a)-208.1(n)-3.3(ovel)-212.4(typ)-5.4(e)-203.9(of)-209.2(HPV)-212.7(v)1.9(accine)]TJ 0 -1.3921 TD 0.0105 Tc [(t)3.8(o)-535.2(t)3.8(r)2.8(eat)-531.6(H)2(PV-relat)3.8(ed)-527.8(carcin)3.5(ogen)3.5(esis.)-527.4(F)1.4(ilm)-531.8(m)-2.7(a)10.5(t)-6.4(erials)-532.6(m)3.6(a)0.3(ke)-531(th)10.5(e)]TJ 0 -1.3858 TD 0 Tc [(ad)24.7(mi)20(ni)19.9(st)23.5(ra)26.2(ti)20.3(o)15(n)-498.4(of)-487.7(th)20.4(e)-497.4(H)0(P)18.1(V)-499.8(v)17.1(a)0(c)21.5(c)0(i)20.9(n)0(e)-485.5(e)0(a)21.5(s)0(y)-488.2(a)0(n)20.5(d)-500.5(re)24.1(du)19.5(c)12.9(e)-497.4(th)20.4(e)-497.4(r)0(i)19.3(s)0(k)-488.7(o)15(f)]TJ T* -0.0212 Tc [(ch)5.9(oking)-344.3(o)0.1(r)-343.8(s)2.6(uf)61.9(focati)5.7(on)-349.5(i)5.7(n)-349.5(ped)-5.1(i)5.7(atric,)-344.9(geri)5.7(atric,)-344.9(and)-345.3(p)1.2(sychiatri)5.7(c)-348.5(patients)]TJ 0 -1.3921 TD 0 Tc (\()Tj 0.85098 0.19216 0.2 scn 0.3213 0 TD -0.0192 Tc [(16)6.3(0)]TJ 0.15294 0.15294 0.15294 scn 1.3732 0 TD -0.0215 Tc [(\).)-238.1(The)]TJ /F9 1 Tf 2.4882 0 TD 0 Tc ()Tj /F8 1 Tf 0.5102 0 TD -0.0215 Tc [(lm)-236.3(dosage)-235.4(forms)-237(i)-0.9(ncorporated)-238.5(w)0.4(ith)-240.1(D)2(NA-)-234.4(a)-0.3(nd)-238.5(VLP)5.1(-)-1.4(based)]TJ -4.6929 -1.3858 TD -0.0222 Tc [(vaccines)-458.2(of)60.9(fer)-458.2(a)-460.8(promisi)4.7(n)-4(g)-458.7(a)5.4(p)-6.1(p)0.2(r)]TJ 12.7055 0 TD -0.0218 Tc [(oach)-460.9(f)-1.7(o)5.8(r)-457.8(future)-456.2(HPV)-458.7(d)0.6(evelopment.)]TJ -12.7055 -1.3921 TD -0.0214 Tc [(While)-449.5(i)-0.8(ntramuscular)-444.8(injection)-450.5(o)-0.1(f)-448.5(H)1.6(PV)-445.7(vaccines)-444.8(has)-451.1(s)2.4(hown)-444.2(clinical)]TJ 0 -1.3858 TD -0.0209 Tc [(ef)68.5(fec)4.5(t)-2.4(iven)3.6(ess,)-262.7(t)3.9(h)-0.1(e)-260(e)4.5(f)]TJ /F9 1 Tf 7.1055 0 TD 0 Tc ()Tj /F8 1 Tf 0.5102 0 TD -0.0202 Tc [(c)5.2(a)1.1(cy)-255.1(of)-258.3(orally)-261.4(adm)4.4(i)0.4(ni)6.7(st)4.6(ered)-256.1(HPV)-255.5(v)-3.1(a)7.4(cci)6.7(nes)-254.6(r)3.6(em)4.4(ains)]TJ -7.6157 -1.3921 TD 0.0312 Tc [(un)5.3(ce)-6.3(rtain.)-550.8(Additional)-550.3(research)-552.8(is)-556(needed)-557.5(to)-552.3(investigate)-554.4(t)-0.7(he)]TJ 0 -1.3858 TD 0.0109 Tc [(bioavailability,)-533.3(i)0(mmune)-530.6(r)-3.1(e)10.9(s)-9.1(ponse,)-533.3(and)-527.4(s)-3.1(afety)-532.7(a)0.7(spec)10.9(t)-8.1(s)-532.2(of)-529.6(orally)]TJ 0 -1.3921 TD -0.0215 Tc [(admi)5.4(nistered)-301.5(HPV)-300.9(v)1.9(accines)-300(i)-0.9(n)-299.4(p)0.9(recl)]TJ 13.8583 0 TD -0.021 Tc [(i)5.9(n)-2.8(ical)-300.1(studies)-293.2(and)-301(c)4.4(linical)-300.1(t)3.8(ri)5.9(als.)]TJ /F1 1 Tf 10.5001 0 0 10.5001 304.8944 757.7573 Tm 0 Tc [(4.5.2)-298.8(Dosing)-305.3(regimens)]TJ /F8 1 Tf 9 0 0 9 318.8409 745.2849 Tm [(For)-411.3(novel)-411.4(HPV)-412.5(vaccines,)-417.3(reducing)-410.5(the)-414(vaccination)-414.6(frequency)]TJ -1.5496 -1.3921 TD [(would)-506.2(be)-507.6(a)-507.9(wise)-506.6(st)-8(rategy)-9.1(.)-506.4(T)0(o)-504.9(ach)-8.1(ieve)-509.8(this)-10.7(,)-500.1(part)-8.5(ici)-8.9(pants)-513.2(will)-509.4(be)]TJ 0 -1.3858 TD [(admini)-10.9(ste)-7.8(red)-507.9(high)-9(er)-505(conc)-10.4(entr)-8.5(ations)-512.5(of)-506.6(HPV)-507(anti)-9.6(gens)-10(.)-500.1(A)-503.6(rece)-13.2(nt)]TJ 0 -1.3921 TD 0.0101 Tc [(study)-508.3(d)-5.3(e)-2.2(monstrated)-509.3(the)-512.5(e)-2.2(f)]TJ /F9 1 Tf 11.3134 0 TD 0 Tc ()Tj /F8 1 Tf 0.5417 0 TD 0.0106 Tc [(cac)10.6(y)-520.1(of)-511(a)-509.9(s)2.9(ingle)-512(d)1.5(ose)-512(o)0.4(f)-511(t)3.9(he)-512(HPV)]TJ -11.8551 -1.3858 TD 0 Tc [(va)-12.1(cc)-12.1(in)-11.6(e)-516.3(i)0(n)-521.8(y)0(o)-12.1(u)0(n)-9.9(g)-518.4(wo)-7.2(m)-6.9(e)0(n)-523.3(i)0(n)-521.8(A)0(f)-11(r)-7.7(ic)-10.6(a)-514.2(\()]TJ 0.85098 0.19216 0.2 scn 15.9937 0 TD [(16)-12.1(1)]TJ 0.15294 0.15294 0.15294 scn 1.4551 0 TD [(\))-9.8(.)-512.7(An)-12.9(ot)-10.6(he)-16.8(r)-511.6(r)-7.7(ep)-15.2(or)-11.6(t)-510.6(h)0(a)-14.7(s)]TJ -17.4488 -1.3858 TD 0.0725 Tc [(sh)5.1(own)-570.8(o)-0.7(ne)-576.1(dose)-569.8(of)-568.8(quadrivalent)-570.4(HPV)-572.2(v)1.4(acci)4.9(natio)5.6(n)-577.1(h)5.1(a)-0.7(d)]TJ 0 -1.3921 TD 0.0136 Tc [(com)-5.9(p)4.5(arable)-515.3(ef)58.9(fe)-5(ctive)-5(n)0.3(ess)-516.9(a)-2.9(s)-510.6(t)0.6(wo)-513.2(or)-510.6(three)-515.3(d)-1.8(ose)-5(s)-510.6(in)-516.3(pre)-5(v)-0.8(enting)]TJ 0 -1.3858 TD 0 Tc [(cervical)-422.3(intraepithelial)-425.6(neoplasia)-426.1(\()]TJ 0.85098 0.19216 0.2 scn 13.9087 0 TD (162)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-428(More)-417.7(studies)-428.8(to)-420(compare)]TJ -15.3449 -1.3921 TD [(the)-199.8(ef)]TJ /F9 1 Tf 2.0976 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(cacy)-206.8(among)-200(the)-206.1(one-dose,)-208.8(two-dose,)-205.7(and)-202.8(three-dose)-207.5(regimens)]TJ -2.6268 -1.3858 TD [(ar)-11.6(e)-516.3(p)0(r)-10.5(e)0(s)-13.7(e)-12.3(n)-7(t)-6.7(ed)-519.1(in)]TJ 0.85098 0.19216 0.2 scn 7.4961 0 TD 0.0119 Tc [(Ta)11.9(bl)11.9(e)-506.4(6)]TJ 0.15294 0.15294 0.15294 scn 3.2441 0 TD 0 Tc [(.)-512.7(T)-9.6(hi)-15.3(s)-511.6(i)0(n)-17.9(f)0(o)-9(r)-7.7(m)-6.9(a)-10.2(t)-6.7(i)0(o)-14.8(n)-511(i)-10.9(n)-7(di)-13.7(ca)-10(t)-6.7(e)-12.3(d)-513.1(t)-6.7(ha)-14.7(t)-510.6(t)-6.7(h)-10.7(e)]TJ -10.7402 -1.3921 TD [(potency)-437.5(induced)-441.6(by)-440.4(one)-439.1(dose)-442.5(vaccination)-439.8(was)-443.2(almost)-440.5(similar)-440.4(to)]TJ 0 -1.3858 TD 0.0475 Tc [(that)-545(of)-543.4(two)-548.6(o)-0.5(r)-546(t)3(hree)-544.4(doses)-546(i)-1.2(n)-545.4(p)0.6(reventi)5.1(n)-3.6(g)-546.5(H)1.2(PV)-546.8(i)5.1(n)-3.6(fection.)]TJ 0 -1.3921 TD 0 Tc [(Additionally,)-378(self-boosting)-374(vaccination)-376.8(for)-375.7(HPV)-374.7(could)-376.7(reduce)-377.9(the)]TJ 0 -1.3858 TD [(dosing)-374.3(frequency)-382.9(and)-379.2(improve)-373.9(its)-377.9(lasting)-380.1(ef)58.2(fectiveness)-379.6(by)-377.4(loading)]TJ 0 -1.3921 TD [(HPV)-229.8(antigens)-240(into)-236.4(microparticles.)-236.4(This)-234.1(could)-238.1(be)-236.8(released)-237.4(over)-233.6(time,)]TJ 0 -1.3858 TD [(continuously)-302(boosting)-304.1(its)-296(immune)-305.1(response)-307.1(\()]TJ 0.85098 0.19216 0.2 scn 18.2236 0 TD (167)Tj 0.15294 0.15294 0.15294 scn 1.4425 0 TD (,)Tj 0.85098 0.19216 0.2 scn 0.5165 0 TD (168)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD (\).)Tj -20.0693 -1.3921 TD [(Th)17.4(e)-434.4(c)12.9(ur)21(re)24.1(nt)-423.1(HP)18.1(V)-430.6(d)0(o)24.7(s)0(e)-423.1(s)0(c)17.8(h)14.5(ed)16.3(ul)26.7(e)-434.4(r)0(e)17.8(c)12.9(om)20.7(me)24.9(nd)15.3(e)12.8(d)-431.2(by)-421.5(th)20.4(e)-434.4(W)0(H)20.9(O)]TJ -1.5496 -1.3858 TD [(S)14.5(t)0(r)23.5(a)0(t)20.9(e)0(g)17.3(i)14.3(c)-283.2(A)13(dv)20.5(is)19.3(o)15(r)0(y)-274.1(G)15.1(ro)19.9(up)-270.2(of)-267.3(Ex)15.8(p)16.1(e)0(r)17.8(t)0(s)-266.3(o)0(n)-269.2(I)0(m)17.4(m)0(u)21.8(n)0(i)19.9(z)12.9(at)20.9(io)23(n)-284.2(\()15.4(SA)21.1(GE)16.5(\))-280.6(i)14.3(s)-278.5(a)0(s)]TJ 0 -1.3921 TD [(f)13.8(o)0(l)19.3(l)16.9(ow)17.9(s:)-293.6(1\))-299.3(On)20.2(e)-308.4(o)0(r)-295.1(t)0(w)21.5(o)0(-)22.5(d)0(o)18.4(s)0(e)-297.2(s)0(c)24.1(h)0(e)21(d)0(u)19.5(l)0(e)-297.8(f)13.8(or)-301.3(th)20.4(e)-302.1(p)0(r)14.7(i)14.3(ma)20.7(ry)-299.3(ta)20.9(rg)22(e)12.8(t)-309(o)15(f)-313.7(gi)25.1(rl)21.9(s)]TJ 0 -1.3858 TD -0.0162 Tc [(ag)-16.2(ed)-226.9(9)]TJ /F12 1 Tf 2.4756 0 TD 0 Tc ()Tj /F8 1 Tf 0.5039 0 TD [(1)12.9(4)-213.9(ye)23.6(ar)19.9(s;)-199.1(2\))-204.8(On)20.2(e)-213.9(o)15(r)-215.5(t)0(w)21.5(o)0(-)22.5(d)0(o)18.4(s)0(e)-202.7(s)0(c)24.1(h)0(e)21(d)0(u)19.5(l)0(e)-203.3(f)13.8(or)-200.6(yo)19.4(un)21.6(g)-216(w)15.6(om)20.7(en)-202(ag)19.4(e)12.8(d)]TJ -2.9795 -1.3921 TD -0.0129 Tc (15)Tj /F12 1 Tf 0.9323 0 TD 0 Tc ()Tj /F8 1 Tf 0.4976 0 TD [(20)-251.4(ye)17.3(a)15(r)0(s)22.5(;)-267(3)12.9(\))-261.7(Tw)24.9(o)-262.2(d)0(o)18.4(s)0(e)24.1(s)-259.6(wi)17.3(th)-250.5(a)-262.2(6)12.9(-)13.8(m)0(o)20.7(n)0(t)17.8(h)-256.4(in)19.9(te)18.8(rv)22(a)14.9(l)-266.5(f)13.8(o)0(r)-250.9(w)0(o)24.3(m)0(e)18.6(n)-259(ol)19.3(de)22.6(r)]TJ -1.4299 -1.3858 TD 0.0263 Tc [(than)-541.4(2)-4.9(1)-540.4(ye)-4.9(ars)-542(\()]TJ 0.85098 0.19216 0.2 scn 7.1055 0 TD 0.0249 Tc [(16)-6.3(9)]TJ 0.15294 0.15294 0.15294 scn 1.5181 0 TD 0.0279 Tc [(\).)-541.5(Som)-4.2(e)-538.8(expert)-4(s)-534.1(s)-4.9(uggest)-539.4(that)-539.4(single-dose)]TJ -8.6236 -1.3921 TD 0 Tc [(va)19.4(cc)13.1(in)13.6(ati)16.3(on)-489.7(is)-491(le)17.2(ss)-494(ex)14.7(pe)16.3(nsi)18.6(ve,)-482.8(sup)18.2(po)12.1(rt)17.2(s)-499(m)0(o)14.4(r)0(e)-492.4(c)0(o)15.2(mpl)19.8(ian)22.3(ce)13.1(,)-500.1(a)0(n)14.2(d)-500.5(is)]TJ 0 -1.3858 TD [(th)26.7(er)17.8(e)12.9(f)0(o)22.5(r)0(e)-391.6(l)0(o)19.3(g)0(i)25.1(s)0(t)17.2(i)14.3(c)12.8(a)0(l)19.3(l)0(y)-388.1(e)0(a)21.5(s)0(i)19.3(e)12.9(r)-404.5(c)12.9(om)20.7(pa)18.4(re)24.1(d)-399.7(w)0(i)17.3(t)0(h)-389(m)0(u)21.8(l)0(t)22.9(i)0(p)17.8(l)16.9(e)-402.9(d)0(o)18.4(s)0(e)24.1(s)0(,)-394.4(m)0(a)27(k)0(i)18.3(n)0(g)]TJ 0 -1.3921 TD [(i)14.3(t)-201.9(mo)20.7(re)-190.1(f)13.8(e)12.8(as)19.9(ib)23(le)-190.7(to)-187(va)19.4(c)12.9(c)0(i)20.9(n)0(a)20.5(t)0(e)-189.1(m)0(o)20.7(r)0(e)-190.1(w)0(o)24.3(m)0(e)18.6(n)-202.3(i)14.3(n)-202.3(lo)19.3(w)15.6(-)-200.3(an)20.5(d)-198.1(m)0(i)20(d)0(d)19.5(l)0(e)23.5(-)0(i)21.9(n)0(c)18.4(o)0(m)20.7(e)]TJ 0 -1.3858 TD [(c)12.8(o)15(un)15.3(tr)23.5(ie)20.9(s)-316.3(\()]TJ 0.85098 0.19216 0.2 scn 4.2394 0 TD [(17)19.4(0)]TJ 0.15294 0.15294 0.15294 scn 1.4047 0 TD [(\).)-308.3(S)14.5(i)0(m)20(i)0(l)18.7(a)15(rl)21.9(y,)-306.7(th)20.4(e)-308.4(J)0(o)15.7(i)14.3(nt)-303.5(Co)22.1(mm)17.7(i)14.3(t)0(t)18.2(e)12.8(e)-314.7(o)15(n)-315.7(V)0(a)19(c)12.9(ci)20.9(na)20.5(ti)20.3(on)-300.7(an)20.5(d)]TJ -5.6441 -1.3921 TD [(Im)23.7(mu)21.8(ni)19.9(z)12.8(a)0(t)20.9(i)0(o)23(n)-303.1(\(J)16.2(C)13.5(V)0(I)22.1(\))-305.8(st)23.5(at)20.9(em)18.6(e)12.9(n)0(t)-297.1(a)15(ls)21.9(o)-306.3(c)12.9(on)20.5(si)19.3(de)22.6(rs)-292.5(th)20.4(e)-302.1(p)0(o)18.4(t)0(e)25.1(n)0(t)17.8(i)14.3(al)-295.7(c)12.8(h)0(a)16.8(n)0(g)22.6(e)]TJ 0 -1.3858 TD 0.0258 Tc [(to)-532.5(a)-538.8(o)-3.3(ne-dose)-534.6(s)-0.8(c)-5.4(h)2.5(edule)-534.6(f)-4.5(or)-542.5(the)-540.9(r)-0.8(outine)-534.6(HPV)-537(i)2.3(mm)-6.3(un)-6.4(ization)]TJ 0 -1.3921 TD -0.018 Tc [(pr)-18(og)-18(r)4(a)-18(m)-299.7(\()]TJ 0.85098 0.19216 0.2 scn 4.0126 0 TD -0.0129 Tc (171)Tj 0.15294 0.15294 0.15294 scn 1.4047 0 TD -0.0154 Tc (\).)Tj /F1 1 Tf 10.5001 0 0 10.5001 304.8944 371.1118 Tm 0 Tc [(4.5.3)-298.8(Expansion)-307.1(of)-300.2(vaccine)-304.3(recipients)]TJ /F8 1 Tf 9 0 0 9 318.8409 358.6393 Tm [(In)-266.2(2018,)-259.7(the)-256.5(FDA)-262.4(approved)-265(the)-262.8(expanded)-262.8(use)-262.2(of)-261(Gardasil)-263.1(9)]TJ /F13 1 Tf 7.4999 0 0 7.4999 530.7589 362.6078 Tm ()Tj /F8 1 Tf 9 0 0 9 538.7526 358.6393 Tm (to)Tj -25.9843 -1.3921 TD [(include)-245.5(individuals)-252.5(27)-251.4(through)-245.9(45)-245.1(years)-247.6(old)-248.1(\()]TJ 0.85098 0.19216 0.2 scn 17.8268 0 TD (172)Tj 0.15294 0.15294 0.15294 scn 1.4362 0 TD [(\).)-251.6(According)-247.4(to)-250(the)]TJ -19.263 -1.3858 TD [(WHO)-449.5(guidelines,)-463.6(HPV)-450.3(vaccination)-458.7(is)-459.5(usually)-451.4(recommended)-459.1(for)]TJ 0 -1.3921 TD [(boys)-237.8(and)-246.9(girls)-237.8(aged)-247.7(11)-238.8(to)-243.7(12,)-241.3(but)-240.2(can)-243.8(be)-243.1(given)-241.8(as)-244.7(early)-241.9(as)-244.7(age)-244.9(9)-239.1(years)]TJ 0 -1.3858 TD [(for)-501.7(the)]TJ /F9 1 Tf 3.4079 0 TD ()Tj /F8 1 Tf 0.5291 0 TD [(rst)-507(dose)-505.5(before)-505.1(sexual)-511.9(contact)-506.4(and)-505.1(exposure)-507.6(to)-501.9(HPV.)]TJ -3.937 -1.3921 TD [(Children)-310.8(between)-309.9(the)-306.9(ages)-309.2(of)-305.1(11)-308.1(to)-306.7(12)-308.1(years)-310.6(are)-307.4(suggested)-314.2(to)-306.7(get)-310.6(2)]TJ 0 -1.3858 TD [(doses)-204.5(of)-198(the)-206.1(HPV)-204.6(vaccine)-205.6(6)-201.3(t)0(o)-205.9(1)0(2)-201(months)-206.7(apart.)-203.9(For)-203.4(teens)-203.5(and)-202.8(young)]TJ T* [(adults)-397.5(at)-394.9(ages)-403.7(15)-396.3(through)-397.1(26,)-398.8(they)-396.9(need)-399.9(three)-402.5(doses)-399.8(of)-399.5(the)-395.1(HPV)]TJ 0 -1.3921 TD [(vacc)-11.6(ine)-11.3(.)-500.1(E)0(a)-8.9(r)0(l)-9.6(y)-505.8(pre)-10.2(ven)-8.6(tio)-8.9(n)-504.7(w)0(i)-7.9(t)0(h)-508.7(the)-508.5(HPV)-513.3(vac)-11.8(cin)-11.3(e)-503.7(i)0(s)-509.8(a)-507.9(safe)-514(and)]TJ 0 -1.3858 TD 0.0332 Tc [(ef)59.6(f)-3.4(e)-4.3(ct)-5(ive)-539.8(w)-1.6(ay)-535.6(to)-537.7(re)-4.3(du)-7.4(ce)-539.8(HP)-3.2(V)-535.9(i)-2.9(n)-5.3(f)2.9(e)-4.3(c)-4.3(t)1.3(ion)-534.5(\()]TJ 0.85098 0.19216 0.2 scn 18.4945 0 TD 0.0312 Tc [(17)-6.3(3)]TJ 0.15294 0.15294 0.15294 scn 1.537 0 TD 0.0413 Tc [(\).)-528.1(S)5.4(t)9.4(u)7(d)0.7(i)11.5(e)3.8(s)-527(h)5.4(a)5.9(v)1.7(e)]TJ ET 0.49804 0.49804 0.49804 scn 49.833 186.406 495.893 17.688 re f 0.63529 0.63529 0.63529 scn 49.606 204.094 496.346 0.22678 re f 545.726 81.978 0.22681 122.117 re f 49.606 81.978 0.22676 122.117 re f 49.833 81.978 495.893 0.28348 re f 95.471 186.406 m 49.833 186.406 l 49.833 186.633 l 95.471 186.633 l 95.471 186.406 l f* 95.471 186.406 0.22676 17.688 re f 95.698 186.406 59.698 0.22676 re f 155.395 186.406 0.28346 17.688 re f 201.827 186.406 m 155.679 186.406 l 155.679 186.633 l 201.827 186.633 l 201.827 186.406 l f* 201.827 186.406 0.22676 17.688 re f 254.324 186.406 m 202.053 186.406 l 202.053 186.633 l 254.324 186.633 l 254.324 186.406 l f* 254.324 186.406 0.22678 17.688 re f 254.551 186.406 235.105 0.22676 re f 489.657 186.406 0.22678 17.688 re f 489.883 186.406 55.842 0.22676 re f 95.471 160.271 m 49.833 160.271 l 49.833 160.554 l 95.471 160.554 l 95.471 160.271 l f* 95.471 160.271 0.22676 26.135 re f 95.698 160.271 59.698 0.28348 re f 155.395 160.271 0.28346 26.135 re f 201.827 160.271 m 155.679 160.271 l 155.679 160.554 l 201.827 160.554 l 201.827 160.271 l f* 201.827 160.271 0.22676 26.135 re f 254.324 160.271 m 202.053 160.271 l 202.053 160.554 l 254.324 160.554 l 254.324 160.271 l f* 254.324 160.271 0.22678 26.135 re f 254.551 160.271 235.105 0.28348 re f 489.657 160.271 0.22678 26.135 re f 489.883 160.271 55.842 0.28348 re f 95.471 134.192 m 49.833 134.192 l 49.833 134.419 l 95.471 134.419 l 95.471 134.192 l f* 95.471 134.192 0.22676 26.079 re f 95.698 134.192 59.698 0.22675 re f 155.395 134.192 0.28346 26.079 re f 201.827 134.192 m 155.679 134.192 l 155.679 134.419 l 201.827 134.419 l 201.827 134.192 l f* 201.827 134.192 0.22676 26.079 re f 254.324 134.192 m 202.053 134.192 l 202.053 134.419 l 254.324 134.419 l 254.324 134.192 l f* 254.324 134.192 0.22678 26.079 re f 254.551 134.192 235.105 0.22675 re f 489.657 134.192 0.22678 26.079 re f 489.883 134.192 55.842 0.22675 re f 95.471 108.113 m 49.833 108.113 l 49.833 108.34 l 95.471 108.34 l 95.471 108.113 l f* 95.471 108.113 0.22676 26.079 re f 95.698 108.113 59.698 0.22675 re f 155.395 108.113 0.28346 26.079 re f 201.827 108.113 m 155.679 108.113 l 155.679 108.34 l 201.827 108.34 l 201.827 108.113 l f* 201.827 108.113 0.22676 26.079 re f 254.324 108.113 m 202.053 108.113 l 202.053 108.34 l 254.324 108.34 l 254.324 108.113 l f* 254.324 108.113 0.22678 26.079 re f 254.551 108.113 235.105 0.22675 re f 489.657 108.113 0.22678 26.079 re f 489.883 108.113 55.842 0.22675 re f 95.471 82.261 0.22676 25.852 re f 155.395 82.261 0.28346 25.852 re f 201.827 82.261 0.22676 25.852 re f 254.324 82.261 0.22678 25.852 re f 489.657 82.261 0.22678 25.852 re f BT /F5 1 Tf 6.9999 0 0 6.9999 49.6063 214.2992 Tm 0.49804 0.49804 0.49412 scn 0 Tc [(TABLE)-306.1(6)-800.1(A)-296.4(summary)-301.4(of)-303.6(one-dose)-306.4(regimen)-294.8(for)-307.4(HPV)-301.2(vaccines.)]TJ /F1 1 Tf 9 0 0 9 54.6519 192.2456 Tm 1 1 1 scn [(locations)-1189.2(Participants)-1191(Vaccines)-1101(Follow-up)-11215.6(Outcomes)-11212.5(References)]TJ /F8 1 Tf 6.9999 0 0 6.9999 59.7543 171.1559 Tm 0.15294 0.15294 0.15294 scn (Tanzania)Tj 6.1553 0.6803 TD [(Schoolgirls)-296.1(aged)]TJ 1.1015 -1.3607 TD (9)Tj /F12 1 Tf 0.4778 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(14)-297.4(years)]TJ 6.8762 1.3607 TD (Cervarix/)Tj -0.2106 -1.3607 TD (Gardasil-9)Tj 7.9209 0.6803 TD [(1)-306.6(year)]TJ 8.091 0.6803 TD [(HPV)-305.5(16)-297.4(IgG)-307.1(positive:)-298.1(99%)-300.6(\(one)-305.8(dose\))-303(vs)-303.8(100%)-299.5(\(two)-300(doses\))-303.5(vs)-295.7(100%)]TJ 11.1039 -1.3607 TD [(\(three)-308.9(doses\))]TJ 22.3455 0.6803 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (163)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.2547 -3.7337 TD (USA)Tj 5.4345 0.6803 TD [(Females)-308.2(aged)-299.1(9)]TJ 0.8666 -1.3526 TD [(to)-299.5(26)-297.4(years)]TJ 8.1234 0.6722 TD [(Gardasil)-4168(1)-306.6(year)]TJ 13.3069 0.6803 TD [(Hazard)-305.7(ratio)-299.5(for)-302.9(histologically)-303.9(con)]TJ /F9 1 Tf 13.8576 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(rmed)-301.6(preinvasive)-300.8(cervical)-303.7(disease:)-309.5(0.64)-296.9(\(one)]TJ -7.759 -1.3526 TD [(dose\))-303(vs)-295.7(0.72)-305(\(two)-300(doses\))-303.5(vs)-303.8(0.66)-296.9(\(three)-300.8(doses\))]TJ 29.1083 0.6722 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (164)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.36 -3.7256 TD (India)Tj 5.6856 0.6803 TD [(Girls)-297.5(aged)-299.1(10)]TJ /F12 1 Tf 5.3373 0 TD ()Tj /F8 1 Tf -4.0658 -1.3607 TD [(18)-297.4(years)]TJ 7.5727 0.6803 TD [(Gardasil)-3989.8(9)-298.5(years)]TJ 13.4608 0.6803 TD [(Vaccine)-307.8(ef)]TJ /F9 1 Tf 4.1954 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-297.8(against)-303(HPV)-305.5(16/18)-297.1(infection:)-304.7(95.4%)-308.3(\(one)-297.7(dose\))-303(vs)-303.8(93.1%)-300.2(\(two)]TJ 5.1915 -1.3607 TD [(doses\))-303.5(vs)-303.8(93.3%)-300.2(\(three)-308.9(doses\))]TJ 25.6661 0.6803 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (165)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj -65.441 -3.0534 TD (Costa)Tj 0.2673 -1.3526 TD (Rica)Tj 5.1025 1.3526 TD [(Women)-302.4(aged)-307.2(18)]TJ 1.1177 -1.3526 TD [(to)-299.5(25)-297.4(years)]TJ 8.0829 0.6803 TD [(Cervarix)-3356.1(11.3)-305(years)]TJ 14.1411 0.6722 TD [(Vaccine)-307.8(ef)]TJ /F9 1 Tf 4.1954 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-297.8(against)-303(HPV16)-303.2(or)-302.3(18)-297.4(infection:)-304.7(82.1%)-308.3(\(one)-297.7(dose\))-303(vs)-303.8(83.8%)]TJ 3.4907 -1.3526 TD [(\(two)-308.1(doses\))-303.5(vs)-295.7(80.2%)-300.2(\(three)-308.9(doses\))]TJ 26.7271 0.6803 TD (\()Tj 0.85098 0.19216 0.2 scn 0.3483 0 TD (166)Tj 0.15294 0.15294 0.15294 scn 1.4335 0 TD (\))Tj /F1 1 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[(DS,)-310.2(et)-302.5(al.)-309.9(Trends)-307.3(in)-308.6(reasons)-310.4(for)-311(human)-309.6(papillomavirus)-308.8(vaccine)-311.9(hesitancy:)-309.2(2010)]TJ /F12 1 Tf 31.7972 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (2020.)Tj /F11 1 Tf -32.3074 -1.1501 TD (Pediatrics)Tj /F8 1 Tf 3.8552 0 TD [(.)-300.3(\(2023\))-305.7(151:e2022060410.)-299.5(doi:)]TJ 0.15294 0.15294 0.15294 scn 12.6023 0 TD (10.1542/peds.2022)Tj /F12 1 Tf 7.3783 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (060410)Tj 0.13725 0.12157 0.12549 scn -23.4146 -1.5712 TD [(9.)-501.7(De)-215.7(Villiers)-216.7(EM,)-222.1(Fauquet)-217.2(C,)-219.4(Broker)-224.1(TR,)-214.4(Bernard)-225.3(HU,)-220.6(Zur)-215.8(Hausen)-226(H.)-212.6(Classi)]TJ /F9 1 Tf 30.5175 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (cation)Tj -31.9835 -1.142 TD [(of)-302.4(papillomaviruses.)]TJ /F11 1 Tf 8.3502 0 TD (Virology)Tj /F8 1 Tf 3.3368 0 TD [(.)-300.3(\(2004\))-297.6(324:17)]TJ /F12 1 Tf 6.0339 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(27.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.1016/j.virol.2004.03.033)Tj 0.13725 0.12157 0.12549 scn -20.5799 -1.5712 TD [(10.)-500.6(Bernard)-265.8(HU,)-269.2(Burk)-263.2(RD,)-269.4(Chen)-269.6(Z,)-266.2(Van)-268.8(Doorslaer)-263.4(K,)-266.1(Zur)-272.4(Hausen)-266.5(H,)-261.2(de)-270.8(Villiers)-265.3(E-)]TJ -0.9314 -1.142 TD [(MJV.)-283.5(Classi)]TJ /F9 1 Tf 4.738 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cation)-281.6(of)-278.1(papillomaviruses)-290.1(\(PVs\))-282.8(based)-281.9(on)-279.2(189)-280(PV)-279.9(types)-280.7(and)-283.8(proposal)-286.9(of)]TJ -5.2725 -1.142 TD [(taxonomic)-307.7(amendments.)]TJ /F11 1 Tf 10.2211 0 TD (Virology)Tj /F8 1 Tf 3.3368 0 TD [(.)-300.3(\(2010\))-305.7(401:70)]TJ /F12 1 Tf 6.042 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(9.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.7942 0 TD (10.1016/j.virol.2010.02.002)Tj 0.13725 0.12157 0.12549 scn -21.9729 -1.5712 TD [(11.)-500.6(Doorbar)-275(J,)-269.9(Egawa)-271.9(N,)-274.1(Grif)]TJ /F9 1 Tf 11.7923 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(n)-268.9(H)0(,)-277.4(Kranjec)-271.2(C,)-276.1(Murakami)-274.9(I.)-275.1(Human)-275(papillomavirus)]TJ -13.2583 -1.142 TD [(molecular)-222.4(biology)-216.5(and)-210.9(disease)-219.7(association.)]TJ /F11 1 Tf 16.8543 0 TD [(Rev)-219.2(Med)-214.3(Virol)]TJ /F8 1 Tf 5.6451 0 TD [(.)-211.3(\(2015\))-216.6(25:2)]TJ /F12 1 Tf 4.9081 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(23.)-217.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.1101 0 TD (10.1002/)Tj -31.0278 -1.142 TD (rmv.1822)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(12)-13.9(.)-510.9(G)-12.8(al)-17.6(l)-17.3(o)-10.2(wa)-19.9(y)-513.9(D)-16.1(A)-9.5(,)-519(L)-11.6(a)0(i)-23.8(m)0(i)-13.3(n)-17.8(s)-518.8(L)-11.6(A)-9.5(.)-519(H)-9.4(u)-14.5(ma)-14.5(n)-528.1(p)0(a)-14.9(p)-14.5(il)-16.5(l)-9.2(o)-10.2(m)-14.1(a)0(v)-20.2(i)0(r)-23.9(u)0(s)-15(e)-13.3(s:)-535.7(sh)-20.2(ar)-17(e)-13.3(d)-516.7(a)-16.6(n)-9.7(d)-516.7(d)-14.5(is)-15.8(t)-13.9(i)0(n)-17(c)-13.2(t)]TJ -0.9314 -1.142 TD 0.0323 Tc [(pathw)4.7(a)-0.5(ys)-535.1(fo)5.9(r)-535.1(p)1.6(atho)5.9(genesis.)]TJ /F11 1 Tf 12.5618 0 TD 0.0319 Tc [(Curr)-527.4(Opin)-538.6(Virol)]TJ /F8 1 Tf 7.3459 0 TD 0.0314 Tc [(.)-536.2(\()1.8(2015\))-532.7(14:87)]TJ /F12 1 Tf 6.3983 0 TD 0 Tc ()Tj /F8 1 Tf 0.5426 0 TD 0.0317 Tc [(92.)-527.8(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.9605 0 TD 0.0312 Tc [(10.)6.2(1)-8.1(016/)]TJ 6.9999 0 0 6.9999 49.6063 482.3999 Tm 0 Tc (j.coviro.2015.09.001)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD 0.0277 Tc [(1)4.6(3)4.6(.)-499.4(Wi)4.2(lli)4.2(a)3.1(mson)-524.7(AL.)-523.7(R)1.9(ec)6.3(ent)-520.7(d)-3(ev)7.9(elopm)5.5(e)-1.8(nt)5.7(s)-523.5(i)-3.9(n)-524.7(h)-0.1(u)5.1(m)-2.6(an)-524.7(p)5.1(a)-5(p)5.1(i)4.2(llom)5.5(avi)4.2(r)-5.2(u)5.1(s)-523.5(\(HPV)3.9(\))]TJ -0.9314 -1.1501 TD 0 Tc (vaccinology.)Tj /F11 1 Tf 5.2158 0 TD (Viruses)Tj /F8 1 Tf 2.8995 0 TD [(.)-300.3(\(2023\))-297.6(15:1440.)-302.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.8362 0 TD (10.3390/v15071440)Tj 0.13725 0.12157 0.12549 scn -16.0201 -1.5712 TD [(14.)-500.6(Wheeler)-275.6(CM,)-265.8(Hunt)-274.4(WC,)-271.9(Cuzick)-272.1(J,)-269.9(Langsfeld)-282.2(E,)-264.8(Pearse)-275.8(A,)-269.4(Montoya)-272.8(GD,)-272.6(et)-270.1(al.)-277.5(A)]TJ -0.9314 -1.142 TD [(population-based)-348.4(study)-338.7(of)-342.9(human)-342(papillomavirus)-349.3(genotype)-341.5(prevalsence)-342.1(in)-341(the)-338.5(United)]TJ T* [(Stat)-13.7(es:)-508.5(bas)-11.1(eline)-514.4(meas)-12(ures)-514.7(prior)-510.9(to)-510.1(mass)-517.6(human)-512.1(pap)-13.3(illom)-9.5(avi)-11.3(rus)-509.5(vacci)-13.5(nation)-18.9(.)]TJ /F11 1 Tf 32.4532 0 TD [(Int)-510.5(J)]TJ -32.4532 -1.142 TD (Cancer)Tj /F8 1 Tf 2.778 0 TD [(.)-300.3(\(2013\))-305.7(132:198)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(207.)-305(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.758 0 TD (10.1002/ijc.27608)Tj 0.13725 0.12157 0.12549 scn -12.6346 -1.5712 TD [(15.)-500.6(Liu)-462.7(F,)-468.8(Chang)-470.9(L,)-465.9(Bai)-469.4(T,)-472(Liu)-462.7(X,)-473.4(Hu)-461.3(J.)-472.4(Association)-471.6(of)-464.4(human)-471.6(papillomavirus)]TJ -0.9314 -1.142 TD [(genotype)-333.4(distribution)-336.7(and)-332.4(cervical)-336.1(cytology:)-335.8(a)-332.4(cross-sectional)-339.9(study.)]TJ /F11 1 Tf 27.7233 0 TD [(Epidemiol)-338.7(Infect)]TJ /F8 1 Tf 6.4955 0 TD (.)Tj -34.2188 -1.142 TD [(\(2021\))-305.7(149:e95.)-300.5(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.253 0 TD (10.1017/S0950268821000741)Tj 0.13725 0.12157 0.12549 scn -7.3216 -1.5712 TD [(16.)-500.6(Kirnbauer)-386.6(R,)-382.9(Booy)-380.7(F,)-387.8(Cheng)-386.6(N,)-379.4(Lowy)-385.3(D,)-389.4(Schiller)-381.9(J.)-383.3(Papillomavirus)-388.3(L1)-383.1(major)]TJ -0.9314 -1.142 TD [(capsid)-414.9(protein)-409.6(self-assembles)-419.8(into)-413.7(virus-like)-411.9(particles)-412.9(that)-412.3(are)-410.9(highly)-411.6(immunogenic.)]TJ /F11 1 Tf T* [(Proc)-298.2(Natl)-305.9(Acad)-296.4(Sci)-306.3(U.S.A)]TJ /F8 1 Tf 10.0834 0 TD [(.)-300.3(\(1992\))-305.7(89:12180)]TJ /F12 1 Tf 6.9977 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(4.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.8023 0 TD (10.1073/pnas.89.24.12180)Tj 0.13725 0.12157 0.12549 scn -19.4622 -1.5712 TD [(17.)-500.6(Graham)-290.9(SV.)-293.6(Human)-291.2(papillomavirus:)-293.3(gene)-291(expression,)-299(regulation)-293.2(and)-291.9(prospects)]TJ -0.9314 -1.1501 TD [(for)-254.3(novel)-256.7(diagnostic)-267(methods)-256.4(and)-259.5(antiviral)-254.7(therapies.)]TJ /F11 1 Tf 21.2683 0 TD [(Future)-256.6(Microbiol)]TJ /F8 1 Tf 6.7142 0 TD [(.)-259.9(\(2010\))-257.1(5:1493)]TJ /F12 1 Tf 5.9529 0 TD ()Tj /F8 1 Tf -33.9354 -1.142 TD [(506.)-305(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.758 0 TD (10.2217/fmb.10.107)Tj 0.13725 0.12157 0.12549 scn -2.8266 -1.5712 TD [(18.)-500.6(Pappa)-285.9(KI,)-281.4(Kontostathi)-284.2(G,)-288.9(Lygirou)-278.3(V,)-291.8(Zoidakis)-286.5(J,)-278(Anagnou)-284.7(NP.)-287.1(Novel)-285.5(structural)]TJ -0.9314 -1.142 TD [(approache)-14(s)-502.6(concerning)-511.9(HPV)-499.9(prote)-11.9(ins:)-504.1(Insight)-507.4(into)-502.8(targeted)-510.7(therapies)-512.6(for)-505.3(cervical)]TJ T* (cancer.)Tj /F11 1 Tf 3.1101 0 TD [(Oncol)-306.1(Rep)]TJ /F8 1 Tf 4.082 0 TD [(.)-300.3(\(2018\))-305.7(39:1547)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(54.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.3892/or.2018.6257)Tj 0.13725 0.12157 0.12549 scn -16.5627 -1.5712 TD [(19.)-500.6(Li)-205.2(Z,)-209.5(Yan)-203.1(X,)-206.1(Yu)-207.6(H,)-204.5(Wang)-212.1(D,)-203.1(Song)-211.7(S,)-204.9(Li)-205.2(Y,)-209.9(et)-205.3(al.)-204.6(The)-212.7(C-terminal)-208.4(arm)-209.3(of)-205.2(the)-200.8(human)]TJ -0.9314 -1.142 TD [(pap)-13.3(ill)-9.4(o)-10.2(mav)-10.1(iru)-14.2(s)-510.7(majo)-9.6(r)-510.7(c)0(a)-13.6(psi)-14.2(d)-508.6(prot)-14.9(ein)-516.2(is)-509.9(im)-13.3(mun)-14.1(oge)-11(nic)-516.2(an)-10.1(d)-508.6(inv)-12.6(olv)-15(ed)-505.7(in)-519.2(vir)-11.4(us-h)-12.8(o)-10.2(s)0(t)]TJ T* (interaction.)Tj /F11 1 Tf 4.8595 0 TD (Structure)Tj /F8 1 Tf 3.6284 0 TD [(.)-300.3(\(2016\))-305.7(24:874)]TJ /F12 1 Tf 6.0339 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(85.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1016/j.str.2016.04.008)Tj 0.13725 0.12157 0.12549 scn -17.3807 -1.5712 TD [(20.)-500.6(Wang)-276.9(JW,)-273.8(Roden)-276.2(RB.)-269.7(L2,)-278.5(the)-273.7(minor)-276.8(capsid)-277.3(protein)-271.9(of)-278.1(papillomavirus.)]TJ /F11 1 Tf 29.9587 0 TD (Virology)Tj /F8 1 Tf 3.3368 0 TD (.)Tj -34.2269 -1.142 TD [(\(2013\))-305.7(445:175)]TJ /F12 1 Tf 6.0015 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(86.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1016/j.virol.2013.04.017)Tj 0.13725 0.12157 0.12549 scn -8.8524 -1.5712 TD [(21.)-500.6(Yim)-295.4(EK,)-303.4(Park)-302.4(JS.)-304.1(The)-301.8(role)-308.5(of)-294.3(HPV)-305.5(E6)-303.5(and)-300(E7)-303.5(oncoproteins)-307.9(in)-300.5(HPV-associated)]TJ -0.9314 -1.142 TD 0.0452 Tc [(cervi)5.5(cal)-547.1(c)7.7(arci)5.5(noge)7.7(ne)7.6(si)5.5(s.)]TJ /F11 1 Tf 11.0796 0 TD 0.0418 Tc [(Ca)-3.7(nc)-4.4(er)-541.8(R)-5(e)-0.6(s)-548.5(T)3.1(r)-7.3(e)-0.6(a)-3.7(t)]TJ /F8 1 Tf 7.9372 0 TD 0.0474 Tc [(.)-544.5(\()9.7(20)8.1(05)8.1(\))-541(3)0(7)8.1(:)6.2(31)8.1(9)]TJ /F12 1 Tf 7.0867 0 TD 0 Tc ()Tj /F8 1 Tf 0.5507 0 TD 0.0463 Tc [(24)7(.)-545.6(d)7.5(oi:)]TJ 0.15294 0.15294 0.15294 scn 4.0658 0 TD 0.0399 Tc [(1)-7.5(0)0.6(.4)-7.5(14)-7.5(3/)]TJ -30.72 -1.1501 TD 0 Tc (crt.2005.37.6.319)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(22.)-500.6(Silva)-216.6(L,)-214.8(Teles)-215.9(AM,)-218.6(Santos)-214.7(JM,)-219.2(Souza)-218.4(de)-214.1(Andrade)-216.4(M,)-217.2(Medeiros)-219.4(R,)-212.8(Faustino-Rocha)]TJ -0.9314 -1.142 TD [(AI,)-292.8(et)-286.3(al.)-293.7(Malignancy)-290(associated)-300.9(with)-287.2(low-risk)-289.5(HPV6)-296.3(and)-291.9(HPV11:)-287.7(a)-291.9(systematic)-291.2(review)]TJ T* [(and)-291.9(implications)-285.9(for)-294.8(cancer)-285.3(prevention.)]TJ /F11 1 Tf 16.1497 0 TD [(Cancers)-289.7(\(Basel\))]TJ /F8 1 Tf 6.0905 0 TD [(.)-292.2(\(2023\))-289.5(15:4068.)-286.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.7876 0 TD (10.3390/)Tj -31.0278 -1.142 TD (cancers15164068)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD 0.0647 Tc [(23.)-494.8(Rusa)7.7(n)-560.6(M)-6(,)-559.6(L)4.5(i)-566.2(Y)1.3(Y)9.4(,)-567.7(H)6.7(a)-0.4(mmer)7.5(m)2(an)-560.6(PS)6.3(.)-559.6(G)-4.8(eno)5.9(m)2(ic)-564.1(l)6.9(a)-0.4(ndscape)-556(o)-2.2(f)-559.5(h)-3.6(uman)]TJ -0.9314 -1.142 TD 0 Tc (papillomavirus)Tj /F12 1 Tf 5.961 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(associated)-309(cancers.)]TJ /F11 1 Tf 7.8157 0 TD [(Clin)-311.2(Cancer)-314.9(Res)]TJ /F8 1 Tf 6.3902 0 TD [(.)-316.5(\(2015\))-305.7(21:2009)]TJ /F12 1 Tf 6.536 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(19.)-314.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.3044 0 TD (10.1158/)Tj -31.0278 -1.142 TD (1078)Tj /F12 1 Tf 1.9195 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (0432.CCR-14)Tj /F12 1 Tf 5.3697 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (1101)Tj 0.13725 0.12157 0.12549 scn -7.3783 -1.5712 TD [(24.)-500.6(Ahmed)-387.1(HG,)-387.4(Bensumaidea)-387.8(SH,)-392.5(Alshammari)-391.6(FD,)-387.7(Alenazi)-386.6(FSH,)-390.9(ALmutlaq)-389.4(BA,)]TJ -0.9314 -1.142 TD [(Alturkstani)-262.6(MZ,)-264(et)-262(al.)-253.2(Prevalsence)-267.7(of)-261.9(human)-261(papillomavirus)-260.2(subtypes)-265.5(16)-256.9(and)-267.6(18)-256.9(among)]TJ T* [(Yemeni)-453.2(patients)-454.1(with)-449.2(cervical)-457.6(cancer.)]TJ /F11 1 Tf 16.0768 0 TD [(Asian)-450.5(Pac)-446.8(J)-449.3(Cancer)-452.6(Prev)]TJ /F8 1 Tf 10.3426 0 TD [(.)-446.1(\(2017\))-451.4(18:1543)]TJ /F12 1 Tf 6.8114 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (8.)Tj -33.741 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.22034/APJCP.2017.18.6.1543)Tj 0.13725 0.12157 0.12549 scn -0.8666 -1.5793 TD [(25.)-500.6(Didierlaurent)-209.6(AM,)-210.5(Morel)-209.2(S,)-204.9(Lockman)-210.3(L,)-206.7(Giannini)-210.1(SL,)-208.5(Bisteau)-211.9(M,)-201(Carlsen)-211.7(H,)-204.5(et)-213.4(al.)]TJ -0.9314 -1.142 TD [(AS04,)-268.9(an)-261.2(aluminum)-270.2(salt-and)-269.6(TLR4)-264.7(agonist-based)-273.2(adjuvant)-268.8(system,)-265.2(induces)-275.6(a)-259.5(transient)]TJ T* [(localized)-244.5(innate)-232.5(immune)-243.2(response)-240.7(leading)-244.3(to)-234.7(enhanced)-239.8(adaptive)-246.1(immunity.)]TJ /F11 1 Tf 30.0073 0 TD [(J)-238.7(Immunol)]TJ /F8 1 Tf 4.2116 0 TD (.)Tj -34.2188 -1.142 TD [(\(2009\))-305.7(183:6186)]TJ /F12 1 Tf 6.4793 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(97.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.4049/jimmunol.0901474)Tj 0.13725 0.12157 0.12549 scn -9.3302 -1.5712 TD [(26.)-500.6(Monie)-273.3(A,)-277.5(Hung)-280.4(CF,)-274.5(Roden)-276.2(R,)-277.6(Wu)-277.6(TC.)-277.6(Cervarix)]TJ /F16 1 Tf 6.5001 0 0 6.5001 202.3936 105.9023 Tm ()Tj /F8 1 Tf 6.9999 0 0 6.9999 208.7433 104.3716 Tm [(:)-276(a)-275.7(vaccine)-279.5(for)-270.5(the)-281.8(prevention)]TJ -22.7343 -1.142 TD [(of)-432(HPV)-435.1(16,)-427.7(18-associated)-438.7(cervical)-433.3(cancer.)]TJ /F11 1 Tf 17.7371 0 TD (Biologics)Tj /F8 1 Tf 3.4178 0 TD [(.)-429.9(\(2008\))-435.2(2:107)]TJ /F12 1 Tf 5.8233 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(13.)-427.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.5393 0 TD (10.2147/)Tj -31.0278 -1.142 TD (btt.s12160259)Tj 0.13725 0.12157 0.12549 scn 37.3937 95.999 TD [(27.)-500.6(Siddiqui)-270(MAA,)-260.6(Perry)-257.7(CM.)-265.8(Human)-258.8(papillomavirus)-268.3(quadrivalent)-265.8(\(types)-261.7(6,)-258.7(11,)-265.7(16,)]TJ -0.9233 -1.142 TD 0.0159 Tc [(18\))-523.9(re)-5.5(c)-5.5(o)-2.4(m)-6.3(b)-2.4(ina)-8.8(n)-1.9(t)-516.3(v)-3.9(a)]TJ 8.6175 0 TD 0.0216 Tc [(cci)6.2(ne)-510(\(Gardasi)6.2(l)]TJ /F13 1 Tf 5.5001 0 0 5.5001 410.8534 754.866 Tm 0 Tc ()Tj /F8 1 Tf 6.9999 0 0 6.9999 415.1054 752.3715 Tm 0.0215 Tc (\).)Tj /F11 1 Tf 1.1177 0 TD 0.0222 Tc [(Dr)5.5(ugs)]TJ /F8 1 Tf 2.4378 0 TD 0.0231 Tc [(.)-520.2(\()9.7(20)8(06)8(\))-516.7(6)8.1(6:)6.2(1)8(2)-0.1(6)8.1(3)]TJ /F12 1 Tf 7.2163 0 TD 0 Tc ()Tj /F8 1 Tf 0.5264 0 TD 0.0207 Tc [(71)5.6(.)-514.5(d)-1.9(oi)5.3(:)]TJ 0.15294 0.15294 0.15294 scn 3.8471 0 TD 0.0232 Tc [(1)8.2(0)0(.)6.3(2)8.1(16)8.2(5/)]TJ -30.8901 -1.142 TD 0 Tc (00003495)Tj /F12 1 Tf 3.8309 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (200666090)Tj /F12 1 Tf 4.3087 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (00008)Tj 0.13725 0.12157 0.12549 scn -8.2368 -1.5712 TD [(28.)-508.6(Mc)-11.1(Co)-10.3(rmac)-12(k)-507.2(PL.)-511.3(Qu)-12.6(adri)-14.6(val)-13.2(ent)-506.6(hu)-10(man)-518.3(pap)-13.3(ill)-9.4(omav)-12.2(iru)-14.2(s)-502.6(\()0(t)-11(ypes)-517.9(6,)-509.8(11,)-516.7(16,)-508.6(18\))]TJ -0.9233 -1.142 TD 0.0405 Tc [(r)7.6(e)-5.2(comb)6(inant)-540.3(v)4.5(accin)6.5(e)-539.7(\(Gardasil)]TJ /F13 1 Tf 5.5001 0 0 5.5001 401.9526 727.8801 Tm 0 Tc ()Tj /F8 1 Tf 6.9999 0 0 6.9999 406.3747 725.3857 Tm 0.0393 Tc [(\):)-544.5(a)-536.1(r)-1.7(e)-6.4(v)3.3(iew)-539.1(o)-3.3(f)-536.3(i)-8.5(ts)-536.2(use)-540.9(i)-0.4(n)-545.5(t)1.1(he)-540.9(prev)-4.8(ention)-537.4(of)]TJ -14.4974 -1.142 TD 0 Tc [(premalignant)-355.8(anogenital)-369.3(lesions,)-359.1(cervical)-360.4(and)-356.7(anal)-359.8(cancers,)-367.4(and)-356.7(genital)-357(warts.)]TJ /F11 1 Tf 31.8782 0 TD (Drugs)Tj /F8 1 Tf 2.3407 0 TD (.)Tj -34.2188 -1.142 TD [(\(2014\))-297.6(74:1253)]TJ /F12 1 Tf 5.9934 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(83.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1007/s40265-014-0255-z)Tj 0.13725 0.12157 0.12549 scn -8.8605 -1.5712 TD [(29.)-500.6(Signorelli)-266.5(C,)-259.9(Odone)-264.6(A,)-269.4(Ciorba)-255.5(V,)-267.5(Cella)-258.8(P,)-264.8(Audisio)-266.4(R,)-261.4(Lombardi)-263.4(A,)-261.3(et)-262(al.)-269.4(Human)]TJ -0.9233 -1.1501 TD [(papillomavirus)-478.9(9-valent)-488.7(vaccine)-482(for)-481(cancer)-479.6(prevention:)-485.6(a)-478.2(systematic)-485.6(review)-486.7(of)-480.6(the)]TJ 0 -1.142 TD 0.0668 Tc [(availabl)-7.2(e)-562(e)-3.2(vidence.)]TJ /F11 1 Tf 9.4436 0 TD 0.066 Tc [(Epidemio)-8.6(l)-561.6(I)-6(nfect)]TJ /F8 1 Tf 7.7266 0 TD 0.0636 Tc [(.)-568.8(\()-6.5(20)-8.1(17)-8.1(\))-565.3(1)-8.1(45:)-10(196)-8.1(2)]TJ /F12 1 Tf 8.5284 0 TD 0 Tc ()Tj /F8 1 Tf 0.575 0 TD 0.0693 Tc [(82)5.7(.)-563.1(d)-2(oi)5.3(:)]TJ 0.15294 0.15294 0.15294 scn 4.2763 0 TD 0.0644 Tc [(1)-7.3(0)0.8(.1)-7.3(017)-7.3(/)]TJ -30.5499 -1.142 TD 0 Tc (S0950268817000747)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(30.)-500.6(Linton)-265(D,)-259.8(Taylor)-260.4(S.)-261.6(The)-253.2(human)-269.1(papillomavirus)-260.2(vaccine)-263.3(expanded)-268.4(to)-259(middle)-259.2(age)]TJ -0.9233 -1.142 TD (adults.)Tj /F11 1 Tf 2.9076 0 TD [(J)-303.5(Nurse)-304.2(Pract)]TJ /F8 1 Tf 5.3211 0 TD [(.)-300.3(\(2019\))-305.7(15:530)]TJ /F12 1 Tf 6.042 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(1.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.7942 0 TD (10.1016/j.nurpra.2019.04.006)Tj 0.13725 0.12157 0.12549 scn -16.6518 -1.5712 TD [(31.)-500.6(Soliman)-222.8(M,)-225.3(Oredein)-226.7(O,)-217.4(Dass)-228(CR.)-221(Update)-218.5(on)-222.5(safety)-226.6(and)-219(ef)]TJ /F9 1 Tf 24.2488 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-216.8(of)-221.4(HPV)-224.5(vaccines:)]TJ -25.7066 -1.142 TD 0.0581 Tc [(focus)-566(o)-0.7(n)-559.1(g)-2.2(a)-7(r)0.9(d)-5(a)1.1(s)-7.2(i)2.2(l.)]TJ /F11 1 Tf 9.0791 0 TD 0.6198 Tc [(I)564(n)559.6(tJM)555.3(o)561.4(lC)564.5(e)553.2(l)559.1(lM)563.4(e)561.3(d)]TJ /F8 1 Tf 9.4031 0 TD 0.0555 Tc [(.)-568.8(\()-6.5(20)-8.1(21)-8.1(\))-565.3(1)0(0)-8.1(:)-1.9(1)-8.1(0)-0.1(1)]TJ /F12 1 Tf 7.3378 0 TD 0 Tc ()Tj /F8 1 Tf 0.5669 0 TD 0.0629 Tc [(3.)-553.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.677 0 TD 0.0637 Tc [(10)8.2(.)6.3(2)0(20)8.2(88)8.2(/)]TJ -30.064 -1.142 TD 0 Tc (IJMCM.BUMS.10.2.101)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(32.)-500.6(Tang)-428.4(X,)-424.8(Jones)-432.6(TE,)-428.3(Jiang)-428(W,)-425.8(Austin)-428(M,)-427.8(He)-419.5(Y,)-428.6(Li)-423.9(L,)-425.4(et)-432.1(al.)-423.3(Extended)-434.3(Human)]TJ -0.9233 -1.142 TD [(Papillomavirus)-339.7(genotype)-341.5(distribution)-344.8(in)-341(cervical)-344.2(intraepithelial)-342.2(neoplasia)-349(and)-340.5(cancer:)]TJ T* [(analysis)-209.7(of)-213.3(40,352)-213.7(cases)-214.1(from)-219.8(a)-210.9(large)-213.2(academic)-222.3(gynecologic)-210.9(center)-217.8(in)-211.4(China.)]TJ /F11 1 Tf 29.6995 0 TD [(J)-214.4(Med)-214.3(Virol)]TJ /F8 1 Tf 4.5193 0 TD (.)Tj -34.2188 -1.1501 TD [(\(2023\))-297.6(95:e28302.)-306.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 9.2087 0 TD (10.1002/jmv.28302)Tj 0.13725 0.12157 0.12549 scn -8.2854 -1.5712 TD [(33.)-500.6(Li)-334.8(M,)-330.6(Zhao)-336.4(C,)-332.8(Zhao)-336.4(Y,)-331.4(Wei)-332.2(L.)-336.3(Immunogenicity,)-337.1(ef)]TJ /F9 1 Tf 22.305 0 TD ()Tj /F8 1 Tf 0.5265 0 TD [(cacy,)-339(and)-332.4(safety)-331.9(of)-334.8(human)]TJ -23.7548 -1.142 TD 0.0221 Tc [(p)7.6(a)-2.6(pil)4.8(l)-3.3(omavirus)-521(vaccine)-7.4(:)-521.2(d)-0.5(a)5.6(t)0.1(a)-520.9(f)-2.8(rom)-518.5(C)-2.2(hina)5.5(.)]TJ /F11 1 Tf 18.8143 0 TD 0.0211 Tc [(Fro)-4.9(n)1.4(t)-519.2(I)-2.3(mmu)-6.7(nol)]TJ /F8 1 Tf 6.6413 0 TD 0.0231 Tc [(.)-520.2(\()1.6(202)8.1(3)0(\))-524.8(1)-0.1(4)8(:)-1.9(1112)8.1(750.)]TJ -25.4556 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.3389/)Tj /F9 1 Tf 3.4178 0 TD ()Tj /F8 1 Tf 0.5264 0 TD (mmu.2023.1112750)Tj 0.13725 0.12157 0.12549 scn -4.819 -1.5712 TD [(34.)-500.6(Li)-213.3(J,)-221.3(Shi)-215.1(LW,)-210.6(Li)-213.3(K,)-217.5(Huang)-216(LR,)-216.4(Li)-213.3(JB,)-213.4(Dong)-218(YL,)-213.5(et)-213.4(al.)-220.8(Comparison)-213.4(of)-213.3(the)-217(safety)-218.5(and)]TJ -0.9233 -1.142 TD [(persistence)-245.7(of)-245.7(immunogenicity)-255.6(of)-245.7(bivalent)-245.8(HPV16/18)-246.2(vaccine)-247.1(in)-243.8(healthy)-249.9(9)]TJ /F12 1 Tf 29.3108 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (14-year-old)Tj -29.821 -1.142 TD [(and)-494.4(18)]TJ /F12 1 Tf 2.9481 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(26-year-old)-499.7(Chinese)-493.1(females:)-497.4(A)-495.5(randomized,)-495.4(double-blind,)-498.7(non-inferiority)]TJ -3.4583 -1.142 TD [(clinical)-296.3(trial.)]TJ /F11 1 Tf 5.2644 0 TD (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-300.3(\(2023\))-305.7(41:7212)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(19.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1016/j.vaccine.2023.10.041)Tj 0.13725 0.12157 0.12549 scn -17.7452 -1.5712 TD [(35.)-500.6(Hu)-477.5(YM,)-466.9(Guo)-475(M,)-468.3(Li)-472.5(CG,)-467.1(Chu)-471.7(K,)-476.7(He)-468.1(WG,)-471(Zhang)-477.2(J,)-472.4(et)-472.6(al.)-471.9(Immunogenicity)]TJ -0.9233 -1.142 TD [(noninferiority)-436(study)-427.8(of)-432(2)-436.2(doses)-427.8(and)-437.7(3)-428.1(doses)-435.9(of)-432(an)-431.3(Escherichia)-432.2(coli-produced)-437.5(HPV)]TJ T* [(bivalent)-237.7(vaccine)-247.1(in)-243.8(girls)-247.8(vs.)-247.8(3)-241.8(doses)-241.5(in)-243.8(young)-244.4(women.)]TJ /F11 1 Tf 21.1711 0 TD [(Sci)-241.5(China)-247.8(Life)-243(Sci)]TJ /F8 1 Tf 6.8357 0 TD [(.)-243.6(\(2020\))-240.9(63:582)]TJ /F12 1 Tf 5.9205 0 TD ()Tj /F8 1 Tf -33.9273 -1.142 TD [(91.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1007/s11427)Tj /F12 1 Tf 6.1796 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (019-9547)Tj /F12 1 Tf 3.7094 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (7)Tj 0.13725 0.12157 0.12549 scn -13.2583 -1.5793 TD [(36.)-500.6(Chen)-261.5(Q,)-257.9(Zhao)-255.4(H,)-261.2(Yao)-260.3(X,)-254.7(Lin)-263.5(Z,)-258.1(Li)-253.8(J,)-261.8(Lin)-255.5(B,)-260(et)-262(al.)-253.2(Comparing)-263(immunogenicity)-263.7(of)]TJ -0.9233 -1.142 TD [(the)-395.1(Escherichia)-399.8(coli-produced)-405.1(bivalent)-399.7(human)-398.7(papillomavirus)-397.9(vaccine)-401(in)-397.7(females)-399.5(of)]TJ T* [(dif)66.7(ferent)-302.3(ages.)]TJ /F11 1 Tf 5.8395 0 TD (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-300.3(\(2020\))-297.6(38:6096)]TJ /F12 1 Tf 6.5117 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(102.)-305(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.758 0 TD (10.1016/j.vaccine.2020.07.030)Tj 0.13725 0.12157 0.12549 scn -18.7981 -1.5712 TD [(37.)-500.6(Qiao)-412.8(YL,)-399.7(Wu)-407.2(T,)-407.2(Li)-407.7(RC,)-407.2(Hu)-412.7(YM,)-402.1(Wei)-405.1(LH,)-410.5(Li)-407.7(CG,)-402.3(et)-407.8(al.)-407.1(Ef)]TJ /F9 1 Tf 26.2331 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy,)-403.8(safety,)-413.6(and)]TJ -27.6909 -1.142 TD [(im)-13.3(mu)-12.5(n)-9.7(o)0(g)-13.9(e)0(n)-14.9(i)0(c)-12.4(i)0(t)-13(y)-513.9(o)-10.2(f)-510.8(an)-520.4(E)-13(s)0(c)-13.7(h)0(e)-16.8(ric)-21(hi)-10.8(a)-518.7(col)-16.5(i-)-17.7(pr)-15(odu)-23.2(ce)-10.3(d)-516.7(b)0(i)-9.4(v)-11.7(al)-17.6(en)-14.9(t)-507.9(h)-11.6(um)-12.5(an)-520.4(pa)-14.9(pi)-13.7(l)-9.2(l)-9.2(o)0(m)-16.3(a)0(v)-12.1(i)0(r)-15.8(u)0(s)]TJ T* [(vaccine:)-336.9(an)-342.2(interim)-341.4(analysis)-339.3(of)-334.8(a)-340.5(randomized)-340.9(clinical)-344.9(trial.)]TJ /F11 1 Tf 23.941 0 TD [(J)-335.9(Natl)-338.3(Cancer)-347.3(Inst)]TJ /F8 1 Tf 7.3378 0 TD [(.)-332.7(\(2020\))]TJ -31.2789 -1.142 TD (112:145)Tj /F12 1 Tf 3.0939 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(53.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1093/jnci/djz074)Tj 0.13725 0.12157 0.12549 scn -5.9529 -1.5712 TD [(38.)-500.6(Guo)-272.5(J,)-269.9(Guo)-272.5(S,)-269.7(Dong)-274.7(S.)-269.7(Ef)]TJ /F9 1 Tf 11.6951 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy,)-266.1(immunogenicity)-279.8(and)-275.7(safety)-267.1(of)-278.1(HPV)-265(vaccination)]TJ -13.153 -1.142 TD [(in)-511.1(Ch)-11.7(ine)-14.1(se)-515.9(po)-16.7(pu)-12.9(la)-9.5(ti)-13(on:)-514.7(a)-510.6(m)0(e)-11.2(t)0(a)-14.2(-)0(a)-10.8(n)-9.7(al)-9.5(ys)-12.2(is.)]TJ /F11 1 Tf 17.3564 0 TD [(Fr)-15(ont)-521.3(Pu)-10.4(bl)-10.9(ic)-513.2(Hea)-13.1(l)-12.1(t)0(h)]TJ /F8 1 Tf 8.4069 0 TD [(.)-510.9(\()0(2)-12.2(0)0(2)-13.9(3)0(\))-514.4(1)0(1)-13.9(:11)-14.6(287)-12.8(17)-13.9(.)]TJ -25.7633 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.3389/fpubh.2023.1128717)Tj 0.13725 0.12157 0.12549 scn -0.8747 -1.5712 TD [(39.)-500.6(Turner)-323.5(TB,)-310.2(Huh)-319.1(WK.)-310.5(HPV)-321.7(vaccines:)-313.1(translating)-320.1(immunogenicity)-320.3(into)-316.5(ef)]TJ /F9 1 Tf 31.0359 0 TD ()Tj /F8 1 Tf 6.9999 0 0 6.9999 532.2896 396.3968 Tm (cacy.)Tj /F11 1 Tf -32.4856 -1.142 TD [(Hum)-297.8(Vaccin)-298.8(Immunother)]TJ /F8 1 Tf 10.3588 0 TD [(.)-300.3(\(2016\))-297.6(12:1403)]TJ /F12 1 Tf 6.5117 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(5.)-307.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.8023 0 TD (10.1080/21645515.2015.1103936)Tj 0.13725 0.12157 0.12549 scn -19.2597 -1.5712 TD [(40.)-500.6(Hu)-453.2(S,)-447.9(Xu)-446.7(X,)-449.1(Zhu)-453.7(F,)-444.5(Hong)-446.2(Y,)-452.9(Hu)-445.1(Y,)-452.9(Zhang)-444.8(X,)-449.1(et)-448.3(al.)-455.7(Ef)]TJ /F9 1 Tf 25.3989 0 TD ()Tj /F8 1 Tf 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[(papill)-14.6(omavi)-11.4(rus)-509.5(\(HPV)-11.1(\))-507.4(infec)-11.7(tion)-510.9(and)-510.6(vacc)-14.4(ination)-18.1(.)]TJ /F11 1 Tf 21.0901 0 TD [(Vacci)-11.8(nes)-506.6(\(B)-10.2(asel\))]TJ /F8 1 Tf 6.6575 0 TD [(.)-502.8(\(20)-11.1(22\))-505.1(10:)-14.6(837.)]TJ -27.7476 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.3390/vaccines10060837)Tj 0.13725 0.12157 0.12549 scn -0.8747 -1.5712 TD [(45.)-500.6(Steele)-437.2(J,)-431.9(Mann)-438.9(C,)-438.1(Rookes)-429.6(S,)-439.8(Rollason)-431.7(T,)-439.6(Murphy)-431.5(D,)-438(Freeth)-431.5(M,)-435.9(et)-432.1(al.)-439.5(T-cell)]TJ -0.9233 -1.142 TD [(responses)-378.8(to)-380.5(human)-382.5(papillomavirus)-381.7(type)-377.4(16)-378.4(among)-386.4(women)-374.7(with)-384.4(dif)66.7(ferent)-383.3(grades)-381.1(of)]TJ T* [(cervical)-303.7(neoplasia.)]TJ /F11 1 Tf 7.5646 0 TD [(Br)-303.2(J)-295.4(Cancer)]TJ /F8 1 Tf 4.6327 0 TD [(.)-300.3(\(2005\))-297.6(93:248)]TJ /F12 1 Tf 6.0339 0 TD ()Tj /F8 1 Tf 0.5102 0 TD 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0.12157 0.12549 scn -15.5665 -1.5712 TD [(62.)-500.6(Farhat)-470.5(S,)-480.3(Nakagawa)-473.2(M,)-476.4(Moscicki)-475.9(A-B.)-474.4(Cell-mediated)-481.7(immune)-478.1(responses)-476(to)]TJ -0.9314 -1.1501 TD [(human)-479.7(papillomavirus)-478.9(16)-467.5(E6)-473.6(and)-478.2(E7)-473.6(antigens)-479.6(as)-470.6(measured)-476(by)-475.6(interferon)-475.8(gamma)]TJ 0 -1.142 TD 0.0547 Tc [(enzyme-linke)-7.1(d)-551.1(i)-1.2(mmunos)5.6(p)-0.3(ot)-550.4(in)-554.4(women)-554.4(w)2.8(ith)-556.3(c)1(lea)5.8(r)-2.5(ed)-551.1(or)-553.2(pers)5.6(istent)-558.5(human)]TJ T* 0.011 Tc [(p)-3.5(a)11(p)-3.9(i)-4.4(lloma)11(v)-9.2(i)11(r)-12.9(u)11(s)-522.4(i)11(n)-6(f)11(e)-10.9(c)-2.3(t)11(i)-10.1(on.)]TJ /F11 1 Tf 10.9743 0 TD 0 Tc [(I)-15.3(n)-11.6(t)-516(J)-522.2(G)-11.4(y)0(n)-20.1(e)-10(c)-13.8(o)-9.8(l)-522.3(C)0(a)-19.9(n)-11.6(ce)-23.7(r)]TJ /F8 1 Tf 9.0953 0 TD [(.)-519(\()-13.4(20)-22(09)-22(\))-515.5(1)-15(9:)-23.8(50)-13.9(8)]TJ /F12 1 Tf 6.5927 0 TD ()Tj /F8 1 Tf 0.5183 0 TD 0.0126 Tc [(12)12.6(.)-513.4(d)-1.9(oi)12.6(:)]TJ 0.15294 0.15294 0.15294 scn 3.7742 0 TD 0 Tc [(10)-22(.1)-15.7(1)-15(1)0(1)-22(/)]TJ -30.9549 -1.142 TD (IGC.0b013e3181a388c4)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(63.)-500.6(Kamolratanakul)-280.5(S,)-285.9(Pitisuttithum)-283.4(P.)-281(Human)-275(papillomavirus)-292.6(vaccine)-279.5(ef)]TJ /F9 1 Tf 29.4727 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(cacy)-281.6(and)]TJ -30.9306 -1.142 TD 0.0456 Tc [(ef)69.3(fe)8(cti)5.9(v)1.5(eness)-546.1(a)]TJ 6.4793 0 TD 0.0432 Tc [(gainst)-545.7(cancer.)]TJ /F11 1 Tf 6.8276 0 TD 0.0409 Tc [(Va)-4.6(c)-5.3(c)2.8(i)-5(n)-3.1(es)-549.4(\(Ba)-4.6(s)1.3(e)-9.5(l)4.5(\))]TJ /F8 1 Tf 7.3135 0 TD 0.0399 Tc [(.)-543.9(\()-5.9(20)-7.5(21)-7.5(\))-548.5(9)0.6(:1)-7.5(41)-7.5(3.)-552(doi)-7.9(:)]TJ 0.15294 0.15294 0.15294 scn 10.0996 0 TD [(1)-7.5(0)0.6(.3)-7.5(39)-7.5(0/)]TJ -30.72 -1.142 TD 0 Tc (vaccines9121413)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD 0.014 Tc [(6)14(4)-8(.)-496.9(V)-1.7(e)14(r)-7.8(ma)14(e)-7.7(l)4.8(en)-506(K.)-513.1(V)14(a)-10.2(cci)14(ne)-509.5(str)14(a)-3(tegie)14(s)-518.1(to)-506.5(im)14(p)-6.6(r)14(o)-12.9(v)2.3(e)-509.5(a)14(nti-ca)14(ncer)-512.9(ce)14(l)-8.4(l)4.8(ula)14(r)-521.4(im)14(m)-6.1(u)-0.5(ne)]TJ -0.9314 -1.142 TD 0 Tc (responses.)Tj /F11 1 Tf 4.3735 0 TD [(Front)-301.5(Immunol)]TJ /F8 1 Tf 6.1553 0 TD [(.)-300.3(\(2019\))-297.6(10:8.)-305.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 7.3945 0 TD (10.3389/)Tj /F9 1 Tf 3.4178 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (mmu.2019.00008)Tj 0.13725 0.12157 0.12549 scn -20.9444 -1.5712 TD [(65.)-500.6(Chabeda)-415(A,)-423.3(Yanez)-416(RJR,)-426.9(Lamprecht)-417.2(R,)-423.4(Meyers)-417.7(AE,)-420.1(Rybicki)-420.9(EP,)-423.6(Hitzeroth)-417.3(II.)]TJ -0.9314 -1.142 TD [(Therapeutic)-217.5(vaccines)-215.2(for)-213.8(high-risk)-220(HPV-associated)-220.1(diseases.)]TJ /F11 1 Tf 23.9248 0 TD [(Papillomavirus)-214.5(Res)]TJ /F8 1 Tf 7.4836 0 TD [(.)-211.3(\(2018\))]TJ -31.4084 -1.1501 TD (5:46)Tj /F12 1 Tf 1.6603 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(58.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1016/j.pvr.2017.12.006)Tj 0.13725 0.12157 0.12549 scn -4.5112 -1.5712 TD [(66.)-500.6(Yang)-255.4(A,)-261.3(Jeang)-255.8(J,)-261.8(Cheng)-257.1(K,)-258(Cheng)-257.1(T,)-253.3(Yang)-263.5(B,)-251.9(Wu)-261.4(T-C,)-255.7(et)-262(al.)-253.2(Current)-263(state)-260.5(in)-251.9(the)]TJ -0.9314 -1.142 TD [(development)-486.1(of)-488.7(candidate)-484.1(therapeutic)-489(HPV)-483.7(vaccines.)]TJ /F11 1 Tf 22.7424 0 TD [(Expert)-485.3(Rev)-486.4(Vaccines)]TJ /F8 1 Tf 8.3907 0 TD [(.)-486.6(\(2016\))]TJ -31.1331 -1.142 TD (15:989)Tj /F12 1 Tf 2.616 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(1007.)-303.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 4.2358 0 TD (10.1586/14760584.2016.1157477)Tj 0.13725 0.12157 0.12549 scn -6.4307 -1.5712 TD [(67.)-500.6(Castro-Eguiluz)-273.5(D,)-267.9(Barquet-Mu駉z)-277.3(SA,)-271.2(Arteaga-Go)]TJ /F15 1 Tf 21.981 0.0405 TD ()Tj /F8 1 Tf 0.081 -0.0405 TD [(mez)-275.5(AC,)-269.4(Salcedo)-273.2(Herna)]TJ /F15 1 Tf 9.5003 0.0405 TD ()Tj /F8 1 Tf 0.0486 -0.0405 TD (ndez)Tj -32.5423 -1.142 TD 0.0191 Tc [(RA)-6.6(,)-516.1(R)-6.7(odr)]TJ /F17 1 Tf 4.1792 0 TD 0 Tc ()Tj /F15 1 Tf 0.2916 0.0405 TD ()Tj /F8 1 Tf -0.0081 -0.0405 TD 0.0206 Tc [(gu)6.1(ez-Trejo)-524.2(A)3(,)-522.7(G)-0.3(allard)6.1(o-Rinco)]TJ /F15 1 Tf 12.8209 0.0405 TD 0 Tc ()Tj /F8 1 Tf 0.1053 -0.0405 TD 0.0205 Tc [(n)-523.8(D)4.4(,)-522.8(e)-0.9(t)-519.8(a)3.9(l.)-522.8(Therapeut)6.6(i)-3(c)-519.2(u)-2.1(se)-519.2(of)-514.6(human)]TJ -17.3888 -1.142 TD 0.0192 Tc [(p)4.7(a)-5.5(p)4.7(i)-4.3(llom)5.1(a)2.6(vi)3.8(ru)4.7(s)-515.8(v)-0.6(acc)5.9(i)-4.3(ne)5.9(s)-515.8(i)-4.3(n)-517(c)5.9(ervi)3.8(cal)-516.4(l)1.9(esi)3.8(o)0.9(ns.)]TJ /F11 1 Tf 19.3083 0 TD 0.0142 Tc [(Rev)-520.7(I)-9.2(nv)-10.5(est)-518(C)-8.7(li)-7.4(n)]TJ /F8 1 Tf 6.6899 0 TD 0.0154 Tc [(.)-519.8(\()-6.1(202)-7.7(0\))-516.3(7)-7.7(2)0.4(:2)-7.7(39)]TJ /F12 1 Tf 6.698 0 TD 0 Tc ()Tj /F8 1 Tf 0.5345 0 TD 0.0151 Tc (49.)Tj -33.2307 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.24875/RIC.20000059)Tj 0.13725 0.12157 0.12549 scn -0.8666 -1.5712 TD [(68)-13.9(.)-510.9(K)-14.3(im)-531.6(D,)-535.2(Ga)-21.3(mb)-16.3(h)-11.6(i)0(r)-23.9(a)-518.7(R)-9.6(,)-519(K)-14.3(a)0(r)-17(a)-16.6(n)-9.7(a)0(m)-532.8(B)0(,)-527.3(M)-14(o)-10.2(n)-9.7(ie)-530.8(A)-9.5(,)-519(H)-9.4(u)-14.5(n)-9.7(g)-522(C-)-18.6(F)-14.5(,)-519(R)-9.6(o)-10.2(d)-14.5(e)0(n)-525.2(R)-9.6(,)-527.1(e)0(t)-529.3(a)0(l)-17.6(.)]TJ -0.9314 -1.142 TD [(Generation)-334.1(and)-340.5(characterization)-339.7(of)-334.8(a)-332.4(preventive)-336(and)-332.4(therapeutic)-343.2(HPV)-329.8(DNA)-331.5(vaccine.)]TJ /F11 1 Tf T* (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-300.3(\(2008\))-305.7(26:351)]TJ /F12 1 Tf 6.042 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(60.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1016/j.vaccine.2007.11.019)Tj 0.13725 0.12157 0.12549 scn -11.9948 -1.5712 TD [(69.)-500.6(Bonam)-447.7(SR,)-441.3(Partidos)-449.1(CD,)-446.1(Halmuthur)-444.6(SKM,)-452(Muller)-449.4(S.)-439.8(An)-448.5(overview)-444(of)-448.2(novel)]TJ -0.9314 -1.1501 TD [(adj)-16(uva)-10.5(nts)-518.1(des)-12.1(ign)-12.6(ed)-513.8(for)-513.4(imp)-11.7(ro)-10.7(vin)-12.6(g)-505.8(vacc)-14.4(ine)-516.2(ef)]TJ /F9 1 Tf 18.9196 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cac)-10.7(y.)]TJ /F11 1 Tf 2.4702 0 TD [(Tren)-20.3(ds)-511.5(Pha)-12.2(rma)-10.2(col)-513.6(Sc)-9.3(i)]TJ /F8 1 Tf 9.1682 0 TD [(.)-502.8(\()0(2)-12.2(017)-12.8(\))]TJ -31.0926 -1.142 TD (38:771)Tj /F12 1 Tf 2.616 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(93.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1016/j.tips.2017.06.002)Tj 0.13725 0.12157 0.12549 scn -5.4669 -1.5712 TD [(70.)-508.6(Zac)-11.9(ha)-12(ria)-510.3(A,)-512.4(Ha)-9.8(rber)-16.4(ts)-508.4(E,)-507.8(Va)-16.1(lenc)-13.1(ia)-509.8(SM,)-518.6(Myer)-15.2(s)-502.6(B)0(,)-511.1(S)-9.8(ande)-13.6(rs)-511.2(C,)-511(Ja)-10.4(in)-511.1(A,)-512.4(et)-513.1(al.)]TJ -0.9314 -1.142 TD [(Optimization)-401.5(of)-399.6(RG1-VLP)-404.3(vaccine)-401(performance)-406.3(in)-397.7(mice)-404.3(with)-392.5(novel)-402.5(TLR4)-402.4(agonists.)]TJ /F11 1 Tf T* (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-300.3(\(2021\))-305.7(39:292)]TJ /F12 1 Tf 6.042 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(302.)-296.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.758 0 TD (10.1016/j.vaccine.2020.11.066)Tj 0.13725 0.12157 0.12549 scn -12.4808 -1.5712 TD [(71.)-516.7(Ma)-14.4(yn)-13.4(ard)-525.6(SK,)-527(Mar)-14.9(sh)-12.1(al)-17.6(l)-511.3(J)0(D)-10(,)-510.9(Ma)-14.4(cG)-9.9(il)-16.5(l)-511.3(R)-9.6(S,)-512.7(Yu)-523.4(L,)-514.5(Ca)-16.6(nn)-521.6(JA)-11.5(,)-510.9(C)0(h)-11.7(e)0(n)-14.9(g)-513.9(LI)-10.7(,)-510.9(e)0(t)-521.2(a)0(l)-9.5(.)]TJ -0.9314 -1.142 TD [(Vaccination)-506.2(with)-497.8(synthetic)-500.2(long)-502.6(peptide)-504.4(formulated)-496.2(with)-505.9(CpG)-497.2(in)-494.9(an)-504.2(oil-in-water)]TJ T* [(emulsion)-224.7(induces)-218.9(robust)-228.1(E7-speci)]TJ /F9 1 Tf 13.2907 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(c)-215.7(CD8)-225.6(T)-220.2(cell)-215(responses)-225(and)-219(TC-1)-221.5(tumor)-223.4(eradication.)]TJ /F11 1 Tf -13.8252 -1.142 TD [(BMC)-301.1(Cancer)]TJ /F8 1 Tf 5.151 0 TD [(.)-300.3(\(2019\))-305.7(19:1)]TJ /F12 1 Tf 5.0863 0 TD ()Tj /F8 1 Tf 6.9999 0 0 6.9999 124.8378 94.3937 Tm [(12.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1186/s12885-019-5725-y)Tj 0.13725 0.12157 0.12549 scn 23.3741 95.1405 TD [(72.)-500.6(Nakagawa)-303.1(T,)-293.8(Tanino)-298.1(T,)-293.8(Onishi)-301.8(M,)-290.1(Tofukuji)-306(S,)-294(Kanazawa)-301.3(T,)-293.8(Ishioka)-293.3(Y,)-299(et)-294.4(al.)-293.7(S-)]TJ -0.9233 -1.142 TD 0.0234 Tc [(5)8.4(40956,)-519.9(a)-519.6(C)-0.9(pG)-524(oligon)5.6(ucleotide)-516.3(a)-1.2(nn)5.6(e)-6.1(a)6.9(led)-525.7(t)1.4(o)-521.4(a)-519.6(compl)6.1(e)2.1(me)-6(n)5.6(t)1.4(ary)-522.9(s)6.7(trand)-517.6(w)3.9(ith)-522.8(a)-1.2(n)]TJ T* 0.0154 Tc [(amph)-4.3(iph)-4.3(i)0(lic)-524.3(c)2.1(h)-4.3(a)-1.2(in)-520.8(unit,)-519.8(a)-1.1(c)-6(t)1.5(s)-519.6(a)-1.2(s)-519.6(a)-519.5(potent)-524.9(cance)-6(r)-519.6(vac)-5.9(c)2.1(i)-8.1(n)5.7(e)-524.3(a)-1.2(djuv)-4.4(ant)-516.8(b)-2.9(y)-514.7(t)-6.6(arge)-5.9(ting)]TJ T* 0.0583 Tc [(dr)-7(ai)-5.7(ni)-5.7(ng)-560.9(l)-7.6(y)-2(mph)-568.9(n)0(odes.)]TJ /F11 1 Tf 11.3469 0 TD 0.0605 Tc [(Fro)-6(n)0.3(t)-560.8(I)4.7(mmuno)-6(l)]TJ /F8 1 Tf 7.1434 0 TD 0.0636 Tc [(.)-552.6(\()1.6(202)8.1(1\))-557.2(12)8.1(:8)8.1(030)8.1(9)-0.1(0.)-552.6(doi:)]TJ 0.15294 0.15294 0.15294 scn 12.1082 0 TD 0.0565 Tc [(10)-7.1(.3)-7.2(3)-7.1(8)1(9)-7.2(/)]TJ /F9 1 Tf -30.5985 -1.142 TD 0 Tc ()Tj /F8 1 Tf 0.5264 0 TD (mmu.2021.803090)Tj 0.13725 0.12157 0.12549 scn 0.3969 -1.5712 TD [(73.)-508.6(Gable)-13.5(h)-505.7(F)0(,)-509.3(Saei)-14.6(di)-507.8(M,)-508.8(Hemat)-10.6(i)-501.3(S)-9.9(,)-502.8(Hamd)-14.2(i)-501.3(K)0(,)-509.1(Sole)-10.2(iman)-15.3(jahi)-506.3(H)-9.4(,)-502.8(Gorji)-517.9(A,)-504.3(et)-505(al)-9.5(.)]TJ -0.9233 -1.142 TD 0.0161 Tc [(C)16.1(o)-10.4(mbination)-512(o)-2.2(f)-519(t)2.2(he)-515.5(t)-5.9(o)5.9(ll)-511.4(lik)-5.1(e)-515.5(rece)-5.3(ptor)-510.8(agon)6.4(ist)-516.1(a)-0.5(nd)]TJ /F14 1 Tf 22.5156 0 TD 0 Tc (a)Tj /F8 1 Tf 0.6398 0 TD 0.0158 Tc [(-Galactosylceramide)-515.8(a)-0.8(s)-519.2(a)-0.8(n)]TJ -23.1554 -1.1501 TD 0 Tc (ef)Tj /F9 1 Tf 0.6398 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cient)-486.7(adjuvant)-495.6(for)-489.1(cancer)-487.7(vaccine.)]TJ /F11 1 Tf 14.7566 0 TD [(J)-489.8(BioMed)-491.8(Sci)]TJ /F8 1 Tf 5.475 0 TD [(.)-486.6(\(2016\))-491.9(23:1)]TJ /F12 1 Tf 5.4507 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(11.)-492.4(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.6527 0 TD (10.1186/)Tj -31.0197 -1.142 TD (s12929)Tj /F12 1 Tf 2.7537 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (016-0238)Tj /F12 1 Tf 3.7094 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (3)Tj 0.13725 0.12157 0.12549 scn -6.5603 -1.5712 TD [(74.)-500.6(Chandra)-239.7(J,)-229.4(Teoh)-231.1(SM,)-235.2(Kuo)-233.5(P,)-232.4(Tolley)-233.4(L,)-231(Bashaw)-235(AA,)-238.4(Tuong)-234.2(ZK,)-231.9(et)-229.6(al.)-237(Manganese-)]TJ -0.9233 -1.142 TD 0.0562 Tc [(do)5.5(p)-6.9(e)2.4(d)-557.7(s)-1(ilica-b)5.5(a)-0.8(sed)-557.7(n)-2.1(anoparticles)-559.8(promote)-556.4(t)1.8(he)-556.4(ef)]TJ /F9 1 Tf 22.8558 0 TD 0 Tc ()Tj /F8 1 Tf 0.5912 0 TD 0.0535 Tc [(cacy)-557.6(o)-5.3(f)-562.6(ant)-9(i)-2.4(ge)-8.4(n-)-5.6(spe)-8.4(c)-0.2(i)]TJ /F9 1 Tf 9.9862 0 TD 0 Tc ()Tj /F8 1 Tf 0.5831 0 TD (c)Tj -34.0164 -1.142 TD (immunotherapy.)Tj /F11 1 Tf 6.9977 0 TD [(J)-295.4(Immunol)]TJ /F8 1 Tf 4.2763 0 TD [(.)-300.4(\(2021\))-305.7(206:987)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(98.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.4049/jimmunol.2000355)Tj 0.13725 0.12157 0.12549 scn -20.6528 -1.5712 TD [(75.)-500.6(Granadillo)-260.5(M,)-257.7(Batte)-252.1(A,)-261.3(Alfonso)-252.5(AB,)-261.5(Blanco)-253.5(A,)-253.2(Urquiza)-262.9(D,)-251.7(Varas)-260.4(L,)-255.3(et)-253.9(al.)-253.2(Impact)]TJ -0.9233 -1.142 TD [(on)-279.2(antitumor)-278.9(response)-289.3(using)-286.8(a)-275.7(new)-285.5(adjuvant)-285(preparation)-287.7(as)-276.2(a)-283.8(component)-287.3(of)-278.1(a)-283.8(human)]TJ T* [(papillomavirus)-454.6(type)-450.3(16)-451.3(therapeutic)-456.6(vaccine)-457.7(candidate.)]TJ /F11 1 Tf 22.8233 0 TD (Vaccine)Tj /F8 1 Tf 3.1101 0 TD [(.)-446.1(\(2019\))-459.5(37:3957)]TJ /F12 1 Tf 6.8195 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (60.)Tj -33.2631 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1016/j.vaccine.2019.05.060)Tj 0.13725 0.12157 0.12549 scn -0.8747 -1.5712 TD [(76.)-500.6(Mo)-226.8(Y,)-226.1(Ma)-225(J,)-221.3(Zhang)-226.2(H,)-228.8(Shen)-222.7(J,)-221.3(Chen)-229.1(J,)-221.3(Hong)-227.5(J,)-229.4(et)-221.5(al.)-220.8(Prophylactic)-232.4(and)-227.1(therapeutic)]TJ -0.9233 -1.142 TD [(HPV)-354.1(vaccines:)-369.8(current)-357.2(scenario)-362.9(and)-364.8(perspectives.)]TJ /F11 1 Tf 20.4746 0 TD [(Front)-358.2(Cell)-356.7(Infect)-361.5(Microbiol)]TJ /F8 1 Tf 10.7799 0 TD [(.)-357(\(2022\))]TJ -31.2545 -1.1501 TD [(12:909223.)-300(doi:)]TJ 0.15294 0.15294 0.15294 scn 6.3659 0 TD (10.3389/fcimb.2022.909223)Tj 0.13725 0.12157 0.12549 scn -5.4426 -1.5712 TD [(77.)-500.6(Alvarez)-252.2(RD,)-245.2(Huh)-246.2(WK,)-253.8(Bae)-248.6(S,)-245.4(Lamb)-247(LS,)-249(Conner)-246(MG,)-246.2(Boyer)-254.6(J,)-245.6(et)-245.8(al.)-245.1(A)-252.5(pilot)-249.5(study)]TJ -0.9233 -1.142 TD [(of)-440.1(pNGVL4a-CRT/E7\(detox\))-459.7(for)-440.6(the)-451.8(treatment)-449.2(of)-440.1(patients)-454.1(with)-441.1(HPV16)-449(+)-448.5(cervical)]TJ T* [(intraepithelial)-228.8(neoplasia)-219.4(2/3)-226.5(\(CIN2/3\).)]TJ /F11 1 Tf 15.3641 0 TD [(Gynecol)-231.1(Oncol)]TJ /F8 1 Tf 5.6613 0 TD [(.)-227.5(\(2016\))-224.7(140:245)]TJ /F12 1 Tf 6.3659 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(52.)-217.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.1182 0 TD (10.1016/)Tj -31.0197 -1.142 TD (j.ygyno.2015.11.026)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(78.)-500.6(Chandra)-255.9(J,)-261.8(Woo)-251.2(W,)-255.7(Finlayson)-259.7(N,)-249.8(Liu)-260.3(H,)-253.1(McGrath)-252.8(M,)-257.7(Ladwa)-257.1(R,)-253.3(et)-253.9(al.)-253.2(A)-252.5(phase)-259(1,)]TJ -0.9233 -1.142 TD [(single)-408.1(centre,)-412.8(open)-412.3(label,)-407.4(escalating)-419.7(dose)-411.1(study)-411.6(to)-404.8(assess)-412.4(the)-411.3(safety,)-413.6(tolerability)-414.8(and)]TJ T* 0.0219 Tc [(i)6.5(m)-8.4(munogenicity)-524.4(of)-529.4(a)-521.1(t)-0.1(he)-7.6(r)5.2(a)-2.8(pe)-7.5(utic)-517.8(h)-5.9(u)-0.7(man)-522.4(p)-0.7(apillomav)-6.1(i)6.5(rus)-529.3(\()0.4(HP)-7.3(V\))-517.9(DNA)-522.2(v)-6.1(a)5.3(c)-7.5(cine)]TJ T* 0 Tc [(\(A)-14.8(MV)-21.7(00)-13.9(2)-15(\))-515.5(fo)-18.9(r)-518.8(H)-9.4(PV)-20.7(-)-10.5(a)0(s)-17(s)0(o)-18.8(c)0(i)-20.5(a)0(t)-14.2(e)-13.3(d)-516.7(h)-11.6(ea)-13.6(d)-516.7(a)-16.6(n)-9.7(d)-516.7(n)-9.7(e)0(c)-18.4(k)-515.3(c)-13.2(a)0(n)-18.2(c)-13.3(er)-524(\()-13.4(H)-9.4(NC)-14.3(\))-13.4(.)]TJ /F11 1 Tf 27.3751 0 TD [(Ca)-11.8(n)-11.7(c)-13.8(e)-10(r)-510.7(I)-15.3(m)0(m)-17.4(u)-11.6(no)-13.4(l)]TJ -27.3751 -1.142 TD (Immunother)Tj /F8 1 Tf 4.9972 0 TD [(.)-300.3(\(2021\))-297.6(70:743)]TJ /F12 1 Tf 6.0338 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(53.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1007/s00262)Tj /F12 1 Tf 6.1796 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (020-02720)Tj /F12 1 Tf 4.1873 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (7)Tj 0.13725 0.12157 0.12549 scn -25.2855 -1.5712 TD [(79.)-500.6(Hasan)-271.5(Y,)-266.6(Furtado)-271.1(L,)-271.5(Tergas)-262.8(A,)-269.4(Lee)-273.1(N,)-266(Brooks)-269.6(R,)-269.5(McCall)-264.7(A,)-269.4(et)-270.1(al.)-261.3(A)-268.7(phase)-275.2(1)-266.1(trial)]TJ -0.9233 -1.142 TD [(assessing)-303.5(the)-298(safety)-307.6(and)-300(tolerability)-309.5(of)-302.4(a)-300(therapeutic)-310.8(DNA)-299.1(vaccination)-307.8(against)-303(HPV16)]TJ 0 -1.1501 TD [(and)-381(HPV18)-376.1(E6/E7)-382.2(oncogenes)-383.6(after)-384.9(chemoradiation)-386(for)-375.8(cervical)-384.7(cancer.)]TJ /F11 1 Tf 29.5537 0 TD [(Int)-381(J)-376.4(Radiat)]TJ -29.5537 -1.142 TD [(Oncol)-298(Biol)-305.7(Phys)]TJ /F8 1 Tf 6.293 0 TD [(.)-300.3(\(2020\))-305.7(107:487)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(98.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1016/j.ijrobp.2020.02.031)Tj 0.13725 0.12157 0.12549 scn -15.6718 -1.5712 TD [(80.)-500.6(Hillemanns)-342(P,)-337.7(Denecke)-335.1(A,)-334.2(Woelber)-336(L,)-336.3(B鰄mer)-341.5(G,)-337.5(Jentschke)-333.7(M,)-338.7(Schjetne)-337.1(KW,)]TJ -0.9233 -1.142 TD [(et)-221.5(al.)-228.9(A)-228.2(therapeutic)-229.8(antigen-presenting)-235.8(cell-targeting)-226.9(DNA)-226.2(vaccine)-230.9(VB10.16)-230.7(in)-219.5(HPV16-)]TJ T* [(positive)-362.2(high-grade)-368.6(cervical)-368.5(intraepithelial)-374.6(neoplasia:)-373.9(results)-368.1(from)-365.6(a)-364.8(phase)-364.3(I/IIa)-372.1(trial.)]TJ /F11 1 Tf T* [(Clin)-295(Cancer)-306.8(Res)]TJ /F8 1 Tf 6.3659 0 TD [(.)-300.3(\(2022\))-305.7(28:4885)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(92.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1158/1078)Tj /F12 1 Tf 5.3373 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (0432.ccr-22)Tj /F12 1 Tf 4.6489 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (1927)Tj 0.13725 0.12157 0.12549 scn -26.7514 -1.5712 TD [(81.)-500.6(Choi)-450.4(YJ,)-454.9(Hur)-445.6(SY,)-454.6(Kim)-448.8(T-J,)-452(Hong)-454.3(SR,)-449.5(Lee)-451.2(JK,)-454.3(Cho)-451.2(C-H,)-449.9(et)-448.3(al.)-447.6(A)-455(Phase)-451.9(II,)]TJ -0.9233 -1.142 TD [(Prospective,)-395.7(randomized,)-406.4(multicenter,)-407.1(open-label)-400.2(study)-395.4(of)-399.6(GX-188E,)-401(an)-398.9(HPV)-402.7(DNA)]TJ T* [(vaccine,)-482.7(in)-478.7(patients)-486.5(with)-473.5(cervical)-490(intraepithelial)-479.9(neoplasia)-486.7(3A)-478.1(phase)-485.8(II)-476(study)-484.5(of)-480.6(a)]TJ T* [(th)-17.4(e)-13.3(r)0(a)-17(p)-14.5(eu)-19.7(ti)-21.1(c)-515.4(H)-17.5(PV)-530.9(DN)-14.2(A)-519.8(v)-11.7(a)-16.6(c)0(c)-18.4(i)0(n)-17(e)-523.5(in)-535.4(CI)-15.3(N)-524.5(3)0(.)]TJ /F11 1 Tf 18.7171 0 TD [(C)-14.8(l)-12.1(in)-527.3(Ca)-19.9(n)-11.6(c)0(e)-23.7(r)-518.8(Re)-16.3(s)]TJ /F8 1 Tf 6.9248 0 TD [(.)-519(\()-13.4(20)-22(20)-13.9(\))-523.6(2)0(6)-22(:)0(1)-15.7(6)-15.1(16)]TJ /F12 1 Tf 7.0786 0 TD ()Tj /F8 1 Tf 0.5183 0 TD [(23)-22(.)]TJ -33.2388 -1.1501 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1158/1078)Tj /F12 1 Tf 5.3292 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (0432.CCR-19)Tj /F12 1 Tf 6.9999 0 0 6.9999 395.9999 413.348 Tm ()Tj /F8 1 Tf 0.5103 0 TD (1513)Tj 0.13725 0.12157 0.12549 scn -12.6023 -1.5712 TD [(82.)-500.6(Trimble)-299.1(CL,)-287.8(Morrow)-289.9(MP,)-295(Kraynyak)-296.9(KA,)-291.8(Shen)-287.5(X,)-295.2(Dallas)-294.9(M,)-290.1(Yan)-292.2(J,)-286.1(et)-294.4(al.)-293.7(Safety,)]TJ -0.9233 -1.142 TD (ef)Tj /F9 1 Tf 0.6398 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy,)-476.7(and)-478.2(immunogenicity)-490.4(of)-472.5(VGX-3100,)-483.6(a)-478.2(therapeutic)-480.9(synthetic)-484(DNA)-477.3(vaccine)]TJ -1.1744 -1.142 TD 0.0311 Tc [(ta)6.4(rge)-6.4(t)1(i)7.6(n)-2.9(g)-531.4(h)3.3(uman)-529.4(papil)5.7(l)-2.4(oma)6.4(v)-4.9(ir)6.3(us)-536.3(1)8(6)-534.7(and)-534.2(1)-0.1(8)-526.6(E)1.9(6)-534.7(a)6.4(nd)-526.1(E)-6.2(7)-526.6(proteins)-528.2(for)-536.3(cervical)]TJ T* 0 Tc [(intraepithelial)-455.6(neoplasia)-462.3(2/3:)-453.9(a)-453.9(randomised,)-458.4(double-blind,)-466.3(placebo-controlled)-461.1(phase)]TJ T* [(2b)-292.6(trial.)]TJ /F11 1 Tf 3.4097 0 TD (Lancet)Tj /F8 1 Tf 2.6241 0 TD [(.)-300.3(\(2015\))-305.7(386:2078)]TJ /F12 1 Tf 6.9977 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(88.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.1016/S0140)Tj /F12 1 Tf 5.8071 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (6736\(15\)00239)Tj /F12 1 Tf 5.961 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (1)Tj 0.13725 0.12157 0.12549 scn -28.679 -1.5712 TD [(83.)-500.6(LARVOL.)-389(ISA201/ISA)-383.8(Pharma-LARVOL)-382.2(DELTA)-384(\(2022\).)-379.2(Available)-387.1(online)-383.4(at:)]TJ 0.85098 0.19216 0.2 scn -0.9233 -1.142 TD 0.073 Tc [(h)4.7(ttp)-6.3(s:/)6.2(/)-1.9(del)7.1(t)-5.7(a.l)7.1(a)-0.2(rvo)6.1(l)-1(.com/pro)]TJ 12.9667 0 TD 0.0718 Tc [(duc)-6.2(ts/?Produc)-6.2(tId=e78d6)-8(e)1.9(97-ee7)-8(5)]TJ /F12 1 Tf 15.5017 0 TD 0 Tc ()Tj /F8 1 Tf 0.5831 0 TD 0.0721 Tc (4a91)Tj /F12 1 Tf 2.1625 0 TD 0 Tc ()Tj /F8 1 Tf 0.5831 0 TD 0.0714 Tc (84dd-)Tj -31.7972 -1.142 TD 0.0554 Tc [(03489e467f9e&)-6(P)1.9(rod)-7.7(u)0.4(ctName)-6.4(=ISA201&Inst)]TJ 19.4865 0 TD 0.0561 Tc [(itut)-6.4(ions=+ISA+P)-5.5(h)4(arma&Index=0)]TJ 0.13725 0.12157 0.12549 scn -19.4865 -1.142 TD 0 Tc [(\(Accessed)-302(December)-304.6(7)-298.5(2023\).)]TJ 0.9233 -1.5712 TD [(84.)-500.6(Hatano)-246.5(T,)-253.3(Sano)-248.9(D,)-243.6(Takahashi)-249.4(H,)-245(Oridate)-250.3(N.)-249.8(Pathogenic)-250.3(role)-243.7(of)-245.7(immune)-251.3(evasion)]TJ -0.9233 -1.142 TD [(and)-372.9(integration)-381.4(of)-375.3(human)-374.4(papillomavirus)-389.8(in)-373.4(oropharyngeal)-379.5(cancer.)]TJ /F11 1 Tf 27.8772 0 TD (Microorganisms)Tj /F8 1 Tf 6.3416 0 TD (.)Tj -34.2188 -1.1501 TD [(\(2021\))-297.6(9:891.)-304.6(doi:)]TJ 0.15294 0.15294 0.15294 scn 7.354 0 TD (10.3390/microorganisms9050891)Tj 0.13725 0.12157 0.12549 scn -6.4307 -1.5712 TD [(85.)-500.6(Rosales)-400(R,)-399.1(Lo)]TJ /F15 1 Tf 7.2001 0.0486 TD ()Tj /F8 1 Tf 0.0891 -0.0486 TD [(pez-Contreras)-400.2(M,)-395.4(Rosales)-400(C,)-405.7(Magallanes-Molina)-397.4(J-R,)-403.4(Gonzalez-)]TJ -8.2125 -1.142 TD 0.039 Tc [(V)7.1(e)1.4(rgar)6.1(a)-536.4(R)-3(,)-536.7(A)5.2(rr)6.1(oyo-C)6.6(a)-1.8(zar)6.1(e)1.5(z)-541.2(J)4.6(M,)-536.7(et)-533.7(al)5.5(.)-536.7(R)-3(egres)6.1(s)-2(ion)-537.7(o)4.5(f)-536.6(h)3.1(uman)-529.6(papil)5.5(l)-2.6(oma)6.2(v)-5.1(i)7.4(r)-2(us)]TJ T* 0 Tc [(intraepithelial)-390.8(lesions)-398.9(is)-388.4(induced)-395(by)-394.6(MVA)-395.7(E2)-392.6(therapeutic)-391.8(vaccine.)]TJ /F11 1 Tf 27.5209 0 TD [(Hum)-386.9(Gene)-399.4(Ther)]TJ /F8 1 Tf 6.698 0 TD (.)Tj -34.2188 -1.142 TD [(\(2014\))-297.6(25:1035)]TJ /F12 1 Tf 5.9934 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(49.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1089/hum.2014.024)Tj 0.13725 0.12157 0.12549 scn -8.8605 -1.5712 TD [(86.)-500.6(Harper)-330.1(DM,)-330.5(Nieminen)-323.8(P,)-329.6(Donders)-332.2(G,)-321.3(Einstein)-333.9(MH,)-323.8(Garcia)-334.3(F,)-323(Huh)-327.2(WK,)-326.7(et)-326.8(al.)]TJ -0.9233 -1.142 TD [(The)-245.1(ef)]TJ /F9 1 Tf 2.454 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(cacy)-257.3(and)-251.4(safety)-250.9(of)-245.7(Tipapkinogen)-251.2(Sovacivec)-253.1(therapeutic)-254.1(HPV)-256.9(vaccine)-247.1(in)-251.9(cervical)]TJ -2.9805 -1.142 TD [(intraepithelial)-277.4(neoplasia)-284.2(grades)-275.8(2)-282.3(and)-275.7(3:)-274.9(Randomized)-285.3(controlled)-282.2(phase)-275.2(II)-273.5(trial)-282.2(with)-279.1(2.5)]TJ T* [(years)-277.4(of)-221.4(follow-up.)]TJ /F11 1 Tf 7.6942 0 TD [(Gynecol)-287.8(Oncol)]TJ /F8 1 Tf 5.718 0 TD [(.)-284.1(\(2019\))-281.4(153:521)]TJ /F12 1 Tf 6.4793 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(9.)-283(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.7618 0 TD (10.1016/j.ygyno.2019.03.250)Tj 0.13725 0.12157 0.12549 scn -22.2402 -1.5712 TD [(87.)-500.6(Komdeur)-267.9(FL,)-261.8(Singh)-269(A,)-261.3(van)-264.8(de)-262.7(Wall)-257.5(S,)-261.6(Meulenberg)-271.8(JJM,)-261.6(Boerma)-265.4(A,)-261.3(Hoogeboom)]TJ -0.9233 -1.142 TD [(BN,)-314.7(et)-310.6(al.)-318(First-in-human)-327.6(phase)-315.7(I)-314.9(clinical)-320.6(trial)-314.6(of)-318.6(an)-309.8(SFV-based)-324.4(RNA)-316.9(replicon)-321(cancer)]TJ 0 -1.1501 TD [(vaccine)-498.2(against)-497.4(HPV-induced)-500.4(cancers.)]TJ /F11 1 Tf 16.4736 0 TD [(Mol)-499.5(Ther)]TJ /F8 1 Tf 3.9443 0 TD [(.)-494.7(\(2021\))-500(29:611)]TJ /F12 1 Tf 6.4226 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(25.)-500.5(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.6689 0 TD (10.1016/)Tj -31.0197 -1.142 TD (j.ymthe.2020.11.002)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(88.)-500.6(Park)-261.9(Y-C,)-252.8(Ouh)-259.1(Y-T,)-262.4(Sung)-256.5(M-H,)-261.4(Park)-253.8(H-G,)-260.2(Kim)-262.5(T-J,)-257.6(Cho)-256.8(C-H,)-255.5(et)-262(al.)-253.2(A)-260.6(phase)-259(1/)]TJ -0.9233 -1.142 TD [(2a,)-259.1(dose-escalation,)-273.6(safety)-267.1(and)-259.5(preliminary)-266.7(ef)]TJ /F9 1 Tf 17.8505 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(cacy)-265.4(study)-265.8(of)-261.9(oral)-263.3(therapeutic)-270.3(vaccine)-263.3(in)]TJ -18.385 -1.142 TD [(subjects)-399.3(with)-408.7(cervical)-400.9(intraepithelial)-415.1(neoplasia)-405.7(3.)]TJ /F11 1 Tf 20.3207 0 TD [(J)-400.7(Gynecol)-401.2(Oncol)]TJ /F8 1 Tf 6.5522 0 TD [(.)-405.6(\(2019\))-402.8(30\(6\):e88.)]TJ -26.8729 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.3802/jgo.2019.30.e88)Tj 0.13725 0.12157 0.12549 scn -0.8747 -1.5712 TD [(89.)-500.6(Kawana)-255.3(K,)-249.9(Kobayashi)-253(O,)-249.8(Ikeda)-251(Y,)-250.4(Yahata)-252(H,)-245(Iwata)-251.9(T,)-253.3(Satoh)-248.5(T,)-253.3(et)-245.8(al.)-253.2(Phase)-249.4(I)-250.1(and)]TJ -0.9233 -1.142 TD 0.0315 Tc [(II)-526.4(ra)-9.3(n)5.6(d)-7.3(o)5.1(m)-6.9(ize)-6.1(d)-533.8(clinic)-6.1(al)-528.4(tri)-8.2(a)-1.3(l)-528.4(o)-3(f)-536(a)-1.2(n)-529(o)-3(ral)-528.4(t)-6.7(he)-6(rapeu)-7.3(t)1.4(ic)-532.5(vacc)-6.1(ine)-532.5(t)1.4(argeti)-8.2(n)5.6(g)-539.1(hu)-7.3(man)]TJ T* 0 Tc [(pa)-14.9(pi)-21.8(l)-9.2(l)-9.2(o)0(m)-16.3(a)0(v)-12.1(i)-15.4(ru)-15(s)-518.8(f)0(o)-18.9(r)-518.8(tr)-14.3(e)-13.3(a)0(t)-14.2(m)-14.1(en)-14.9(t)-516(o)-10.3(f)-518.9(c)-13.3(er)-13.7(v)-11.8(i)0(c)-20.5(a)0(l)-527.9(i)0(n)-17(t)0(r)-14.3(a)0(e)-21.7(p)0(i)-21.8(t)0(h)-17.4(e)0(l)-14.3(i)0(a)-15.7(l)-519.4(n)-9.7(e)-13.3(op)-16.7(l)-9.2(a)0(s)-17(i)0(a)-526(2)-517.2(an)-18.2(d)-516.7(3)-15.1(.)]TJ /F11 1 Tf 32.4451 0 TD [(JN)-19.6(CI)]TJ -32.4451 -1.142 TD [(Cancer)-298.7(Spectr)]TJ /F8 1 Tf 5.4507 0 TD [(.)-300.3(\(2023\))-305.7(7:pkad101.)-306.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 9.8485 0 TD (10.1093/jncics/pkad101)Tj 0.13725 0.12157 0.12549 scn -14.376 -1.8628 TD 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[(Improvement)-389.9(of)-391.5(RG1-VLP)-388.1(vaccine)-392.9(performance)-390.1(in)-389.6(BALB/c)-393.1(mice)-388.1(by)-386.5(substitution)-391.9(of)]TJ T* [(alhydrogel)-319.2(with)-311.5(the)-314.2(next)-314(generation)-316.8(polyphosphazene)-320.8(adjuvant)-317.4(PCEP.)]TJ /F11 1 Tf 28.6385 0 TD [(Hum)-314(Vaccines)]TJ -28.6385 -1.142 TD (Immunother)Tj /F8 1 Tf 4.9972 0 TD [(.)-300.3(\(2021\))-305.7(17:2748)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(61.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1080/21645515.2021.1875763)Tj 0.13725 0.12157 0.12549 scn -14.376 -1.5712 TD [(100.)-499.4(Han)-286.8(JE,)-291.1(Wui)-293(SR,)-295.6(Park)-286.2(SA,)-295.5(Lee)-289.3(NG,)-295(Kim)-286.8(KS,)-292.2(Cho)-289.2(YJ,)-292.9(et)-286.3(al.)-293.7(Comparison)-294.4(of)-286.2(the)]TJ -0.9314 -1.1501 TD [(immune)-364.7(responses)-362.6(to)-356.2(the)-362.8(CIA06-adjuvanted)-362.1(human)-358.2(papillomavirus)-365.5(L1)-358.8(VLP)-364.4(vaccine)]TJ 0 -1.142 TD [(with)-473.5(those)-470.7(against)-465(the)-476.1(licensed)-469.8(HPV)-467.5(vaccine)-473.9(Cervarix)]TJ /F16 1 Tf 6.5001 0 0 6.5001 209.1968 478.8849 Tm ()Tj /F8 1 Tf 6.9999 0 0 6.9999 218.8913 477.3542 Tm [(in)-470.6(mice.)]TJ /F11 1 Tf 3.8633 0 TD (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-470.4(\(2012\))]TJ -31.1493 -1.142 TD (30:4127)Tj /F12 1 Tf 3.0939 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(34.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.1016/j.vaccine.2012.04.079)Tj 0.13725 0.12157 0.12549 scn -5.9529 -1.5712 TD [(101.)-499.4(Ebensen)-215.6(T,)-220.9(Delandre)-222.8(S,)-213(Prochnow)-217.8(B,)-219.5(Guzma)]TJ /F15 1 Tf 19.7295 0.0405 TD ()Tj /F8 1 Tf 0.0567 -0.0405 TD [(n)-212.2(CA,)-220.9(Schulze)-222.7(K.)-217.5(The)-212.7(combination)]TJ -20.7176 -1.142 TD 0.0148 Tc [(vac)-6.6(c)1.5(ine)-508.7(a)-1.8(djuv)-5.1(a)14.8(n)-11.5(t)-517.4(s)-1.9(ystem)-517.7(a)-1.8(lum/c-d)-7.8(i)-0.6(-AMP)-516.6(re)]TJ 18.8953 0 TD 0.0159 Tc [(sults)-511(i)0.5(n)-512.2(q)-0.5(uantitative)-507.6(a)-0.7(nd)-517(qual)6.7(itative)]TJ -18.8953 -1.142 TD 0 Tc [(enhanced)-369.4(immune)-372.8(responses)-370.7(post)-371.2(immunization.)]TJ /F11 1 Tf 20.4422 0 TD [(Front)-374.4(Cell)-364.8(Infect)-369.6(Microbiol)]TJ /F8 1 Tf 10.8123 0 TD [(.)-365.1(\(2019\))]TJ -31.2545 -1.142 TD [(9:31.)-305.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.9767 0 TD (10.3389/fcimb.2019.00031)Tj 0.13725 0.12157 0.12549 scn -3.0453 -1.5712 TD [(102.)-499.4(Song)-446.6(Y-C,)-447.2(Huang)-450.8(H-C,)-441.8(Chang)-454.7(CY-Y,)-445.9(Lee)-443.1(H-J,)-451.8(Liu)-446.5(C-T,)-450.1(Lo)-443.1(H-Y,)-448.5(et)-448.3(al.)-447.6(A)]TJ -0.9314 -1.142 TD [(potential)-359.7(herbal)-361.1(adjuvant)-357.9(combined)-360(with)-360.1(a)-356.7(peptide-based)-359.4(vaccine)-360.5(acts)-360(against)-359.7(HPV-)]TJ T* [(related)-445.6(tumors)-442.5(through)-446.8(enhancing)-443.2(ef)59.1(fector)-440.5(and)-445.8(memory)-444.7(T-cell)-445.7(immune)-445.7(responses.)]TJ /F11 1 Tf T* [(Front)-301.5(Immunol)]TJ /F8 1 Tf 6.1553 0 TD [(.)-300.3(\(2020\))-297.6(11:62.)-304.6(doi:)]TJ 0.15294 0.15294 0.15294 scn 7.8724 0 TD (10.3389/)Tj /F9 1 Tf 3.4178 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (mmu.2020.00062)Tj 0.13725 0.12157 0.12549 scn -17.0487 -1.5712 TD [(103.)-499.4(Wang)-438.9(X,)-449.1(Che)-438(Y,)-444.8(Chen)-439.7(B,)-446.3(Zhang)-436.7(Y,)-444.8(Nakagawa)-440.8(M,)-444(Wang)-447(X.)-441(evalsuation)-446.8(of)]TJ -0.9314 -1.1501 TD [(immune)-218.9(responses)-225(induced)-224.9(by)-224.5(a)-219(novel)-216.2(human)-228.6(papillomavirus)-219.7(type)-223.5(16)-216.4(E7)-222.5(peptide-based)]TJ 0 -1.142 TD 0.0221 Tc [(vacci)6.7(ne)-517.6(with)-516(C)5.9(a)-2.5(ndida)-520.9(s)5.4(kin)-514.1(t)0.1(est)-518.2(r)5.4(eagent)-518.2(as)-521(an)-522.2(ad)7.6(juvant)-518.2(i)6.7(n)-522.2(C5)7.1(7BL/6)-519.4(m)-0.1(ice)8.8(.)]TJ /F11 1 Tf 33.2307 0 TD 0.0216 Tc (Int)Tj -33.2307 -1.142 TD 0 Tc (Immunopharmacol)Tj /F8 1 Tf 7.6213 0 TD [(.)-308.4(\(2018\))-297.6(56:249)]TJ /F12 1 Tf 6.042 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(60.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.1016/j.intimp.2018.01.037)Tj 0.13725 0.12157 0.12549 scn -16.5222 -1.5712 TD [(104.)-499.4(Liu)-454.6(C,)-454.3(Chu)-455.5(X,)-457.2(Sun)-455.3(P,)-451.1(Feng)-462.4(X,)-457.2(Huang)-450.8(W,)-458.2(Liu)-454.6(H,)-455.6(et)-456.4(al.)-455.7(Synergy)-457.4(ef)67.2(fects)-462.6(of)]TJ -0.9314 -1.142 TD [(Polyinosinic-polycytidylic)-421.9(acid,)-416.8(CpG)-416.2(oligodeoxynucleotide,)-422.8(and)-421.5(cationic)-415.5(peptides)-415.8(to)]TJ T* [(adjuvant)-220.2(HPV)-224.5(E7)-222.5(epitope)-224.7(vaccine)-222.8(through)-220(preventive)-230.7(and)-219(therapeutic)-229.8(immunization)-219.1(in)]TJ T* 0.0376 Tc [(a)-537.8(T)3.7(C)5.2(-)2.8(1)-536.3(g)1.6(rafted)-535.8(m)7.3(o)-5(u)6.9(s)-3.4(e)-534.5(m)7.3(od)6.9(el.)]TJ /F11 1 Tf 14.1654 0 TD 0.0367 Tc [(Hum)-534.9(V)6.2(acci)7(n)-533.8(I)-2.9(mmunoth)4.1(er)]TJ /F8 1 Tf 11.5089 0 TD 0.0393 Tc [(.)-528.3(\()1.6(20)8.1(18)8.1(\))-532.9(14:)6.2(93)8.1(1)]TJ /F12 1 Tf 6.9734 0 TD 0 Tc ()Tj /F8 1 Tf 0.5426 0 TD 0.0393 Tc [(40)8.1(.)]TJ -33.1902 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1080/21645515.2017.1420446)Tj 0.13725 0.12157 0.12549 scn -0.8666 -1.5712 TD [(105.)-499.4(Naziri)-213(H,)-204.5(Tahamtan)-214(A,)-212.7(Dadmanesh)-210.3(M,)-209.1(Barati)-216.9(M,)-209.1(Ghorban)-209.5(K.)-209.4(Antitumor)-215.2(ef)67.2(fects)]TJ -0.9314 -1.142 TD [(of)-383.4(HPV)-386.5(DNA)-388.2(vaccine)-384.8(adjuvanted)-393.8(with)-384.4(beclin-1)-388.2(as)-381.5(an)-382.7(autophagy)-388.8(inducer)-389(in)-389.6(a)-381(mice)]TJ 0 -1.1501 TD (model.)Tj /F11 1 Tf 3.021 0 TD [(Iran)-299.7(BioMed)-305.5(J)]TJ /F8 1 Tf 5.7099 0 TD [(.)-300.3(\(2019\))-305.7(23:388.)-303.4(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.3583 0 TD (10.29252/ibj.23.6.388)Tj 0.13725 0.12157 0.12549 scn -16.1578 -1.5712 TD [(106.)-499.4(Tse)-460.7(S-W,)-454.2(McKinney)-466(K,)-452.4(Walker)-461.5(W,)-458.2(Nguyen)-464.1(M,)-460.2(Iacovelli)-454.3(J,)-464.3(Small)-455.8(C,)-454.3(et)-464.5(al.)]TJ -0.9314 -1.142 TD [(mRNA-encoded,)-390.6(constitutively)-385.3(active)-383.8(STINGV155M)-387.9(is)-380.3(a)-381(potent)-383.4(genetic)-382.1(adjuvant)-390.3(of)]TJ T* (antigen-speci)Tj /F9 1 Tf 5.2887 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(c)-418.2(CD8+)-414.9(T)-414.6(cell)-409.3(response.)]TJ /F11 1 Tf 10.5775 0 TD [(Mol)-418.5(Ther)]TJ /F8 1 Tf 3.8633 0 TD [(.)-413.7(\(2021\))-419(29:2227)]TJ /F12 1 Tf 6.7466 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(38.)-411.5(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.5069 0 TD (10.1016/)Tj -31.0278 -1.142 TD (j.ymthe.2021.03.002)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(107.)-499.4(Tahamtan)-335.5(A,)-334.2(Ghaemi)-326.8(A,)-334.2(Gorji)-331.6(A,)-334.2(Kalhor)-337.8(HR,)-327.5(Sajadian)-335.2(A,)-334.2(Tabarraei)-334.1(A,)-334.2(et)-334.9(al.)]TJ -0.9314 -1.142 TD [(Antitumor)-271.9(ef)59.1(fect)-267.8(of)-270(therapeutic)-278.4(HPV)-265(DNA)-274.8(vaccines)-271.9(with)-271(chitosan-based)-278.3(nanodelivery)]TJ T* (systems.)Tj /F11 1 Tf 3.6041 0 TD [(J)-295.4(BioMed)-305.5(Sci)]TJ /F8 1 Tf 5.0944 0 TD [(.)-300.3(\(2014\))-305.7(21:69.)-304.6(doi:)]TJ 0.15294 0.15294 0.15294 scn 7.8805 0 TD (10.1186/s12929)Tj /F12 1 Tf 6.1796 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (014-0069-z178)Tj 0.13725 0.12157 0.12549 scn -22.3374 -1.5712 TD [(108.)-499.4(Bi)-323.3(Z,)-322.9(Hong)-324.7(W,)-328.6(Que)-325.5(H,)-317.9(He)-330.5(C,)-324.7(Ren)-324.2(W,)-320.5(Yang)-328.3(J,)-318.5(et)-326.8(al.)-326.1(Inactivated)-324.2(SARS-CoV-2)]TJ -0.9314 -1.142 TD [(induces)-340.4(acute)-330.7(respiratory)-340.5(distress)-334.3(syndrome)-341.9(in)-332.9(human)-333.9(ACE2-transgenic)-339(mice.)]TJ /F11 1 Tf 32.0321 0 TD (Signal)Tj -32.0321 -1.142 TD [(Transduct)-298.9(Target)-308.2(Ther)]TJ /F8 1 Tf 9.0467 0 TD [(.)-300.3(\(2021\))-305.7(6:439.)-304.6(doi:)]TJ 0.15294 0.15294 0.15294 scn 7.8805 0 TD (10.1038/s41392)Tj /F12 1 Tf 6.1715 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (021-00851)Tj /F12 1 Tf 4.1953 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (6)Tj 0.13725 0.12157 0.12549 scn -27.3832 -1.5712 TD [(109.)-499.4(Dillon)-450.5(S,)-447.9(Sasagawa)-448.1(T,)-455.8(Crawford)-451.2(A,)-447.6(Prestidge)-452.5(J,)-448.1(Inder)-450.2(MK,)-450.2(Jerram)-451.8(J,)-456.2(et)-448.3(al.)]TJ -0.9314 -1.142 TD [(Resolution)-454.9(of)-456.3(cervical)-457.6(dysplasia)-455.9(is)-453.2(associated)-454.8(with)-457.3(T-cell)-453.8(proliferative)-459(responses)-451.7(to)]TJ 0 -1.1501 TD [(hu)-10(man)-510.2(pap)-13.3(ill)-9.4(oma)-16.6(vir)-11.4(us)-509.1(ty)-9.4(pe)-505.7(16)-516.1(E2.)]TJ /F11 1 Tf 15.3317 0 TD [(J)-506(Gen)-510.9(Vi)-11.6(rol)]TJ /F8 1 Tf 4.9567 0 TD [(.)-510.9(\(20)-11.1(07\))-513.2(88:)-14.6(803)]TJ /F12 1 Tf 6.4874 0 TD ()Tj /F8 1 Tf 0.5183 0 TD [(13.)-516.8(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.7094 0 TD [(10.1)-13.5(099/)]TJ -31.0035 -1.142 TD (vir.0.82678)Tj /F12 1 Tf 4.3978 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (0)Tj 0.13725 0.12157 0.12549 scn -3.9767 -1.5712 TD [(110.)-499.4(Bergvall)-469.2(M,)-468.3(Melendy)-466.5(T,)-463.9(Archambault)-470.2(J.)-472.4(The)-463.8(E1)-465.5(proteins.)]TJ /F11 1 Tf 26.8891 0 TD (Virology)Tj /F8 1 Tf 3.3287 0 TD [(.)-470.4(\(2013\))]TJ -31.1493 -1.142 TD (445:35)Tj /F12 1 Tf 2.616 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(56.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1016/j.virol.2013.07.020)Tj 0.13725 0.12157 0.12549 scn -5.4669 -1.5712 TD [(111.)-499.4(Mirabello)-276.8(L,)-279.6(Schif)54.6(fman)-275.9(M,)-282(Ghosh)-273.7(A,)-277.5(Rodriguez)-281.3(AC,)-285.6(Vasiljevic)-282.2(N,)-274.1(Wentzensen)]TJ -0.9314 -1.142 TD [(N,)-322.7(et)-318.7(al.)-318(Elevated)-324.2(methylation)-317.9(of)-318.6(HPV16)-319.4(DNA)-323.4(is)-315.5(associated)-325.2(with)-319.6(the)-322.3(development)-324.2(of)]TJ T* 0.0143 Tc [(high)-515.7(g)-5.5(r)14.3(a)-10.8(d)-0.2(e)-517.3(cervical)-513.2(i)-1.1(ntraepithelia)14.3(l)-521.7(neoplasia)14.3(.)]TJ /F11 1 Tf 19.6566 0 TD 0 Tc [(In)-26.9(t)-524.1(J)-530.3(C)-14.8(a)-13.1(n)-11.6(c)-13.8(e)-18.1(r)]TJ /F8 1 Tf 5.4264 0 TD 0.015 Tc [(.)-512.1(\()1.6(2013)15(\))-523.7(132:)15(1)-8.8(412)]TJ /F12 1 Tf 7.6294 0 TD 0 Tc ()Tj /F8 1 Tf 0.5264 0 TD 0.015 Tc [(22)15(.)]TJ -33.2388 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1002/ijc.27750)Tj 0.13725 0.12157 0.12549 scn -0.8666 -1.5712 TD [(112.)-499.4(Malcles)-318.9(M-H,)-318.1(Cueille)-317.8(N,)-314.6(Mechali)-320.1(F,)-314.9(Coux)-318.2(O,)-314.6(Bonne-Andrea)-328.4(C.)-316.6(Regulation)-318.6(of)]TJ -0.9314 -1.142 TD [(bovine)-313.6(papillomavirus)-316.9(replicative)-315.1(helicase)-311.7(E1)-311.6(by)-313.6(the)-314.2(ubiquitin-proteasome)-316.1(pathway.)]TJ /F11 1 Tf 6.9999 0 0 6.9999 288.5102 97.3984 Tm (J)Tj -34.1297 -1.142 TD (Virol)Tj /F8 1 Tf 2.0086 0 TD [(.)-300.3(\(2002\))-305.7(76:11350)]TJ /F12 1 Tf 6.9977 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(8.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.8023 0 TD (10.1128/jvi.76.22.11350)Tj /F12 1 Tf 9.3545 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (11358.2002)Tj 0.13725 0.12157 0.12549 scn 15.2102 95.8532 TD 0.0483 Tc [(11)9(3.)-495(M)10(ech)4.3(a)7.5(l)6.7(i)-542.1(F)1.4(,)-535.5(H)6.5(su)-533.2(C-)5.4(Y)9.2(,)-543.6(C)7.8(a)7.4(st)10.1(ro)-537(A)6.4(,)-535.5(L)4.3(o)5.7(rc)10.7(a)-543.3(T)6.3(,)-535.5(B)-0.4(o)5.7(n)6.2(n)6.2(e)2.6(-)5.4(A)6.4(nd)9.5(re)10.8(a)-543.3(C)7.8(.)-535.5(B)-0.4(o)5.7(v)4.1(i)8.6(n)-1.9(e)]TJ -0.9233 -1.142 TD 0 Tc [(papillomavirus)-333.1(replicative)-339.4(helicase)-336(E1)-335.9(is)-331.7(a)-332.4(target)-337.1(of)-334.8(the)-330.4(ubiquitin)-336.2(ligase)-342(APC.)]TJ /F11 1 Tf 31.5623 0 TD [(J)-335.9(Virol)]TJ /F8 1 Tf 2.6565 0 TD (.)Tj -34.2188 -1.142 TD [(\(2004\))-297.6(78:2615)]TJ /F12 1 Tf 5.9934 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(9.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.8023 0 TD (10.1128/jvi.78.5.2615)Tj /F12 1 Tf 8.3907 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (2619.2004)Tj 0.13725 0.12157 0.12549 scn -17.2835 -1.5712 TD [(114.)-499.4(Diamos)-259.2(AG,)-249.8(Larioses)-257.3(D,)-251.7(Brown)-258.9(L,)-247.2(Kilbourne)-259.4(J,)-253.7(Kim)-254.4(HS,)-254.9(Saxena)-254(D,)-251.7(et)-253.9(al.)-253.2(Vaccine)]TJ -0.9233 -1.142 TD [(synergy)-261.7(with)-262.9(virus-like)-266.1(particle)-258.5(and)-267.6(immune)-259.4(complex)-270.8(platforms)-258.3(for)-262.4(delivery)-267.8(of)-261.9(human)]TJ T* 0.0832 Tc [(pa)-6.2(p)-4.2(i)-5.1(llo)-8(mavi)-5.1(r)-6.4(u)-4.2(s)-581.4(L)-9.4(2)-587.9(a)1.8(n)-7.5(t)4.5(i)-5.1(g)-1.4(en)-7.5(.)]TJ /F11 1 Tf 13.9548 0 TD 0.086 Tc [(Vac)7.4(c)-0.6(ine)]TJ /F8 1 Tf 3.7013 0 TD 0.0881 Tc [(.)-584.8(\()1.8(20)8.3(19\))-581.3(37)8.3(:13)8.3(7)]TJ /F12 1 Tf 7.7185 0 TD 0 Tc ()Tj /F8 1 Tf 0.5993 0 TD 0.0868 Tc [(44)7(.)-586.1(d)-0.6(oi:)]TJ 0.15294 0.15294 0.15294 scn 4.4464 0 TD 0.0882 Tc [(10)8.4(.10)8.4(1)0.2(6/)]TJ -30.4203 -1.142 TD 0 Tc (j.vaccine.2018.11.021)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(115.)-499.4(Gambhira)-462.3(R,)-463.9(Karanam)-460.9(B,)-462.5(Jagu)-466(S,)-456(Roberts)-463.2(JN,)-462.3(Buck)-462.3(CB,)-462.5(Bossis)-456.4(I,)-461.4(et)-456.4(al.)-463.8(A)]TJ -0.9233 -1.1501 TD [(protective)-249.6(and)-259.5(broadly)-251.2(cross-neutralizing)-259.6(epitope)-257.1(of)-245.7(human)-261(papillomavirus)-252.1(L2.)]TJ /F11 1 Tf 31.6433 0 TD [(J)-254.9(Virol)]TJ /F8 1 Tf 2.5755 0 TD (.)Tj -34.2188 -1.142 TD [(\(2007\))-297.6(81:13927)]TJ /F12 1 Tf 6.4712 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(31.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1128/JVI.00936)Tj /F12 1 Tf 7.3864 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (07)Tj 0.13725 0.12157 0.12549 scn -17.235 -1.5712 TD [(116.)-499.4(Alphs)-418(HH,)-416.4(Gambhira)-413.7(R,)-415.3(Karanam)-420.4(B,)-413.9(Roberts)-414.6(JN,)-413.7(Jagu)-417.4(S,)-407.4(Schiller)-422.4(JT,)-409.2(et)-415.9(al.)]TJ -0.9233 -1.142 TD [(Pr)-21.6(o)-10.2(t)0(e)-19(c)-13.3(t)-13.9(i)0(o)-17.5(n)-528.1(ag)-20.2(ai)-23.8(n)-9.7(s)0(t)-532.7(h)-11.6(e)-13.3(t)-13.9(er)-21.8(o)-10.2(l)-9.2(o)-10.3(g)-11.7(o)-10.2(u)-14.5(s)-518.8(h)-11.6(u)-14.5(m)-14.1(an)-528.5(p)-14.5(a)0(p)-23(i)-15.4(l)-9.2(l)-9.2(o)-10.2(m)-14.1(a)0(v)-20.2(i)-15.4(ru)-23.1(s)-518.8(c)-13.2(h)-11.7(a)0(l)-25.7(l)-9.2(e)-13.3(n)-9.7(g)-11.7(e)-523.5(b)-10.2(y)-522(a)-518.7(s)-16.7(y)-11.8(n)-9.7(t)-13.9(h)-11.7(et)-19(i)-15.4(c)]TJ T* [(lipopeptide)-367.5(vaccine)-376.7(containing)-376.8(a)-364.8(broadly)-372.7(cross-neutralizing)-381.1(epitope)-370.5(of)-367.2(L2.)]TJ /F11 1 Tf 30.5823 0 TD [(Proc)-363(Natl)]TJ -30.5823 -1.142 TD [(Acad)-296.4(Sci)-298.2(U.S.A)]TJ /F8 1 Tf 5.9934 0 TD [(.)-300.4(\(2008\))-297.6(105:5850)]TJ /F12 1 Tf 6.9977 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(5.)-299.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.7942 0 TD (10.1073/pnas.0800868105)Tj 0.13725 0.12157 0.12549 scn -15.3722 -1.5712 TD [(117.)-499.4(Pogoda)-222.2(CS,)-213.1(Roden)-219.5(RB,)-213(Garcea)-218.8(RL.)-216.4(Immunizing)-214.4(against)-222.1(anogenital)-215.4(cancer:)-213(HPV)]TJ -0.9233 -1.142 TD (vaccines.)Tj /F11 1 Tf 3.8309 0 TD [(PloS)-299.7(Pathog)]TJ /F8 1 Tf 4.7542 0 TD [(.)-300.3(\(2016\))-305.7(12:e1005587.)-304.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 10.6908 0 TD (10.1371/journal.ppat.1005587)Tj 0.13725 0.12157 0.12549 scn -18.3526 -1.5712 TD [(118.)-499.4(Seitz)-227.6(H,)-228.8(Ribeiro-M黮ler)-234.9(L,)-222.9(Canali)-229.5(E,)-224.3(Bolchi)-230(A,)-228.9(Tommasino)-222.1(M,)-233.4(Ottonello)-225.4(S,)-229.2(et)-221.5(al.)]TJ -0.9233 -1.142 TD [(Robust)-204.9(in)]TJ /F11 1 Tf 4.0172 0 TD (vitro)Tj /F8 1 Tf 2.0491 0 TD [(and)-210.9(in)]TJ /F11 1 Tf 2.7213 0 TD (vivo)Tj /F8 1 Tf 1.8223 0 TD [(neutralization)-212.6(against)-214(multiple)-209.4(high-risk)-211.9(HPV)-208.3(types)-207.8(induced)]TJ -10.6099 -1.142 TD [(by)-337.9(a)-348.6(thermostable)-346(thioredoxin-L2)-348.2(vaccine.)]TJ /F11 1 Tf 17.5022 0 TD [(Cancer)-347.3(Prev)-341.6(Res)-347.5(\(Phila\))]TJ /F8 1 Tf 9.6056 0 TD [(.)-340.8(\(2015\))-346.1(8:932)]TJ /F12 1 Tf 5.6451 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (41.)Tj -33.2631 -1.1501 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1158/1940)Tj /F12 1 Tf 5.3292 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (6207.CAPR-15)Tj /F12 1 Tf 5.9691 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (0164)Tj 0.13725 0.12157 0.12549 scn -13.1935 -1.5712 TD [(119.)-499.4(Khanal)-207.6(S,)-196.8(Ferraris)-207.4(ED,)-200(Zahin)-205.5(M,)-201(Joh)-202.1(J,)-205.1(Ghim)-199.8(S-j,)-200.3(Jenson)-207.5(AB.)-204.8(Targeting)-199.7(synthetic)]TJ -0.9233 -1.142 TD [(H)-9.4(u)-14.5(m)-14.1(a)0(n)-536.5(P)-13(ap)-23(i)-15.4(l)-9.2(l)-17.3(o)-10.2(m)-14.1(a)0(v)-20.2(i)-15.4(r)-16.7(u)0(s)-533.4(\()-13.4(H)-17.5(P)-13(V\))-539.4(L)-11.6(2)-525.3(di)-21.8(s)-16.7(u)0(l)]TJ /F9 1 Tf 17.1378 0 TD ()Tj /F8 1 Tf 0.5426 0 TD 0.0132 Tc [(de-induced)-511.6(N-ter)13.2(m)-9.5(inus)-513.7(conforma)13.2(t)-9.1(i)-2.2(onal)]TJ -17.6804 -1.142 TD 0.0139 Tc [(epi)13.9(t)-7.2(opes)-513(for)-513(p)-0.6(an-HP)-7.2(V)-512.1(vaccine)-517.7(d)-0.6(eve)-7.5(l)4.7(op)13.9(m)-6.7(e)-7.5(nt.)]TJ /F11 1 Tf 19.7214 0 TD 0.0152 Tc [(Exp)-510.1(M)-0.7(o)5.4(l)-515.2(Patho)5.4(l)]TJ /F8 1 Tf 6.8357 0 TD [(.)-511.8(\()-6.2(2)15.3(0)-6.7(15\))-508.3(99:330)]TJ /F12 1 Tf 6.6413 0 TD 0 Tc ()Tj /F8 1 Tf 0.5264 0 TD 0.0151 Tc (4.)Tj -33.7248 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1016/j.yexmp.2015.06.021)Tj 0.13725 0.12157 0.12549 scn -0.8747 -1.5712 TD [(120.)-499.4(Bendz)-245.4(H,)-245(Ruhland)-239.8(SC,)-245.5(Pandya)-236.1(MJ,)-243.5(Hainzl)-243.7(O,)-241.7(Riegelsberger)-244(S,)-245.4(Bra點hle)-241.1(C,)-243.7(et)-237.7(al.)]TJ -0.9233 -1.142 TD [(Human)-283.1(heat)-282.1(shock)-283.7(protein)-288.1(70)-281.2(enhances)-290.5(tumor)-280.1(antigen)-292.8(presentation)-285.4(through)-284.8(complex)]TJ T* [(formation)-342.3(and)-340.5(intracellular)-344.2(antigen)-341.4(delivery)-348.8(without)-342.1(innate)-337.8(immune)-348.5(signaling.)]TJ /F11 1 Tf 32.2345 0 TD [(J)-335.9(Biol)]TJ -32.2345 -1.142 TD (Chem)Tj /F8 1 Tf 2.3083 0 TD [(.)-300.3(\(2007\))-305.7(282:31688)]TJ /F12 1 Tf 7.4755 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(702.)-305(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.758 0 TD (10.1074/jbc.M704129200)Tj 0.13725 0.12157 0.12549 scn -13.1287 -1.5712 TD [(121.)-499.4(Zong)-273(J,)-269.9(Wang)-260.7(C,)-268(Liu)-268.4(B,)-268.1(Liu)-268.4(M,)-265.8(Cao)-269.8(Y,)-266.6(Sun)-269(X,)-262.8(et)-270.1(al.)-269.4(Human)-266.9(hsp70)-267.4(and)-267.6(HPV16)]TJ -0.9233 -1.142 TD [(oE7)-321.8(fusion)-326.4(protein)-328.6(vaccine)-328.1(induces)-324.2(an)-326(ef)59.1(fective)-332.5(antitumor)-327.5(ef)]TJ /F9 1 Tf 24.3784 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (cacy.)Tj /F11 1 Tf 2.2678 0 TD [(Oncol)-330.4(Rep)]TJ /F8 1 Tf 4.1063 0 TD [(.)-324.6(\(2013\))]TJ -31.287 -1.142 TD (30:407)Tj /F12 1 Tf 2.6079 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(12.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.3892/or.2013.2445)Tj 0.13725 0.12157 0.12549 scn -5.475 -1.5793 TD [(122.)-499.4(Maecker)-335.1(HT,)-327.5(Ghanekar)-329.2(SA,)-319.8(Suni)-333(MA,)-323.9(He)-330.5(X-S,)-323.6(Picker)-327.8(LJ,)-330.2(Maino)-325.1(VC.)-324.2(Factors)]TJ -0.9233 -1.142 TD [(af)63.9(fecting)-515.2(the)-500.4(ef)]TJ /F9 1 Tf 6.2606 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(ciency)-505.9(of)-504.9(CD8+)-504(T)-503.7(cell)-506.5(cross-)-11.1(primi)-11.3(ng)-499.4(with)-505.9(exogen)-11.5(ous)-503.1(antig)-10.6(ens.)]TJ /F11 1 Tf 27.3265 0 TD (J)Tj -34.1216 -1.142 TD (Immunol)Tj /F8 1 Tf 6.9999 0 0 6.9999 330.5196 469.3605 Tm [(.)-300.3(\(2001\))-305.7(166:7268)]TJ /F12 1 Tf 6.9977 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(75.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.4049/jimmunol.166.12.7268)Tj 0.13725 0.12157 0.12549 scn -13.5256 -1.5712 TD [(123.)-499.4(Neefjes)-477.3(J,)-472.4(Ovaa)-464.1(H.)-471.8(A)-471.2(peptide)]TJ /F12 1 Tf 14.6351 0 TD ()Tj /F8 1 Tf 0.2187 0 TD [(s)-470.2(perspective)-480.5(on)-465.5(antigen)-471(presentation)-479.7(to)-469.6(the)]TJ -15.7771 -1.142 TD [(immune)-299.9(system.)]TJ /F11 1 Tf 6.9005 0 TD [(Nat)-301.9(Chem)-297(Biol)]TJ /F8 1 Tf 5.9529 0 TD [(.)-300.4(\(2013\))-305.7(9:769)]TJ /F12 1 Tf 5.556 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(75.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1038/nchembio.1391)Tj 0.13725 0.12157 0.12549 scn -21.2764 -1.5712 TD [(124.)-499.4(Haghshenas)-458(MR,)-445.5(Mousavi)-447.5(T,)-447.7(Kheradmand)-457.9(M,)-443.9(Afshari)-451.5(M,)-452.1(Moosazadeh)-452.9(M.)]TJ -0.9233 -1.142 TD (Ef)Tj /F9 1 Tf 0.8018 0 TD ()Tj /F8 1 Tf 0.5426 0 TD [(ca)-13.6(cy)-519.1(o)-10.2(f)-518.9(hu)-10(m)-14.1(a)0(n)-520.4(p)0(a)-14.9(p)-14.5(ill)-17.5(o)-10.2(m)0(a)-14.5(v)-11.7(ir)-15.8(us)-517.2(l)-9.2(1)-517.2(pr)-15(o)-10.2(t)0(e)-10.9(i)0(n)-527.3(v)0(a)-12.1(c)-13.3(ci)-12.4(n)-9.7(e)0(s)-524(\()0(c)-18.5(e)0(r)-13.7(v)-11.7(ari)-16.2(x)-520.1(a)0(n)-18.2(d)-516.7(ga)-12.1(rd)-15(as)-17(il)-16.4(\))-515.5(i)0(n)]TJ -1.3445 -1.142 TD [(reducing)-506.1(the)-508.5(risk)-507.3(of)-504.9(cervical)-506.2(intrae)-12.6(pithelial)-507.8(neoplasi)-16.5(a:)-503.2(a)-502.5(meta-analysis.)]TJ /F11 1 Tf 30.1936 0 TD [(Int)-510.5(J)-497.9(Prev)]TJ -30.1936 -1.142 TD (Med)Tj /F8 1 Tf 1.7656 0 TD [(.)-300.3(\(2017\))-305.7(8\(1\):44.)-298.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.5689 0 TD (10.4103/ijpvm.IJPVM_413_16)Tj 0.13725 0.12157 0.12549 scn -9.4112 -1.5712 TD [(125.)-499.4(Chen)-472.1(J,)-464.3(Ni)-467(G,)-467.1(Liu)-470.8(XS.)-467(Papillomavirus)-469.3(virus)-471.9(like)-464(particle-based)-478(therapeutic)]TJ -0.9233 -1.142 TD [(va)-20.2(cc)-18.4(in)-17(e)-523.5(a)0(g)-20.2(a)0(i)-23.8(n)-9.7(st)-532.7(hu)-18.1(ma)-22.6(n)-520(p)0(a)-14.9(p)-14.5(il)-24.6(l)-9.2(o)-10.3(ma)-14.5(v)-11.8(i)-15.4(ru)-15(s)-526.9(i)0(n)-17(f)0(e)-21.9(c)-13.3(ti)-13.1(o)-10.2(n)-520(r)-16.7(e)0(l)-14.3(a)-16.6(te)-19(d)-516.7(d)-14.5(is)-23.9(ea)-13.6(s)-16.7(e)0(s)-21.8(:)-519(im)-21.4(mu)-20.6(n)-9.7(o)-10.2(l)-9.2(o)-10.3(g)-11.7(i)0(c)-20.5(a)0(l)]TJ T* 0.0244 Tc [(problem)-5.9(s)-526.8(a)-0.3(nd)-524.7(f)-8.6(u)1.8(tu)-6.3(re)-523.4(d)-6.3(i)0.9(rect)-5.7(ions.)]TJ /F11 1 Tf 14.6189 0 TD 0.0273 Tc [(Cel)7.1(l)-527.4(Imm)6.5(unol)]TJ /F8 1 Tf 5.9772 0 TD 0.0235 Tc [(.)-527.9(\()2(20)-7.8(11\))-532.5(269)-7.8(:5)]TJ /F12 1 Tf 6.3092 0 TD 0 Tc ()Tj /F8 1 Tf 0.5345 0 TD 0.0313 Tc [(9.)-520.1(d)8.7(o)4.8(i)7.8(:)]TJ 0.15294 0.15294 0.15294 scn 3.4016 0 TD 0.0235 Tc [(10)-7.7(.10)-7.8(1)0.4(6/)]TJ -30.8415 -1.1501 TD 0 Tc (j.cellimm.2011.03.003)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(126.)-499.4(Simon)-221.4(P,)-224.3(Buxant)-218.7(F,)-217.7(Hallez)-216.7(S,)-221.1(Burny)-223(A,)-220.8(Fayt)-218.7(I,)-218.4(Anaf)-214.6(V,)-218.9(et)-221.5(al.)-220.8(Cervical)-217.6(response)-224.5(to)]TJ -0.9233 -1.142 TD [(vaccination)-259.2(against)-262.5(HPV16)-254.6(E7)-263(in)-260(case)-254.1(of)-261.9(severe)-263.1(dysplasia.)]TJ /F11 1 Tf 23.2121 0 TD [(Eur)-253.9(J)-263(Obstet)-253.9(Gynecol)-263.5(Reprod)]TJ -23.2121 -1.142 TD (Biol)Tj /F8 1 Tf 1.5469 0 TD [(.)-300.3(\(2003\))-305.7(109:219)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(23.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1016/s0301)Tj /F12 1 Tf 5.7018 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (2115\(03\)00093)Tj /F12 1 Tf 5.961 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (9)Tj 0.13725 0.12157 0.12549 scn -23.609 -1.5712 TD 0.023 Tc [(127.)-496(Schwar)6.3(z)-524.8(T)5.3(F,)-520.3(Leo)-521.8(O)0.7(.)-520.3(I)7.7(mmune)-516.7(respons)6.3(e)-524.8(to)-513.7(huma)6.4(n)-521.3(p)0.4(apil)5.7(lomavir)6.3(u)0.4(s)-520.1(a)-1.7(fter)]TJ -0.9233 -1.142 TD 0 Tc [(prophylactic)-306.8(vaccination)-307.8(with)-303.4(AS04-adjuvanted)-316.1(HPV-16/18)-305.3(vaccine:)-304.5(Improving)-313.9(upon)]TJ T* (nature.)Tj /F11 1 Tf 3.102 0 TD [(Gynecol)-295.9(Oncol)]TJ /F8 1 Tf 5.7342 0 TD [(.)-300.3(\(2008\))-305.7(110:S1)]TJ /F12 1 Tf 6.0258 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(S10.)-299.8(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.7499 0 TD (10.1016/j.ygyno.2008.05.036)Tj 0.13725 0.12157 0.12549 scn -18.1987 -1.5712 TD [(128.)-499.4(Einstein)-374.4(MH,)-372.4(Baron)-377.4(M,)-371.1(Levin)-369.6(MJ,)-373(Chatterjee)-372.7(A,)-374.7(Edwards)-370.8(RP,)-371.6(Zepp)-380.8(F,)-371.6(et)-367.3(al.)]TJ -0.9233 -1.142 TD [(Comparison)-367.3(of)-375.3(the)-370.9(immunogenicity)-377(and)-372.9(safety)-372.4(of)-367.2(Cervarix)]TJ /F16 1 Tf 6.5001 0 0 6.5001 473.8959 308.863 Tm ()Tj /F8 1 Tf 6.9999 0 0 6.9999 482.8534 307.3889 Tm [(and)-372.9(Gardasil)]TJ /F13 1 Tf 5.5001 0 0 5.5001 519.3069 309.8834 Tm ()Tj /F8 1 Tf 6.9999 0 0 6.9999 526.0534 307.3889 Tm (human)Tj -31.5947 -1.142 TD [(papillomavirus)-365.5(\(HPV\))-372.7(cervical)-368.5(cancer)-366.2(vaccines)-369.1(in)-365.3(healthy)-371.4(women)-366.6(aged)-363.9(18)]TJ /F12 1 Tf 30.3393 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(45)-370.3(years.)]TJ /F11 1 Tf -30.8496 -1.142 TD [(Hum)-297.8(Vaccin)]TJ /F8 1 Tf 5.0539 0 TD [(.)-300.3(\(2009\))-305.7(5:705)]TJ /F12 1 Tf 5.5641 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(19.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.272 0 TD (10.4161/hv.5.10.9518)Tj 0.13725 0.12157 0.12549 scn -13.477 -1.5712 TD [(129.)-499.4(Herrin)-356.5(DM,)-346.7(Coates)-346(EE,)-350.8(Costner)-347.8(PJ,)-355.9(Kemp)-347.9(TJ,)-344.4(Nason)-350.9(MC,)-346.8(Saharia)-354.3(KK,)-345.2(et)-351.1(al.)]TJ -0.9233 -1.1501 TD [(Comparison)-213.4(of)-205.2(adaptive)-213.7(and)-210.9(innate)-216.3(immune)-210.8(responses)-216.9(induced)-216.8(by)-208.3(licensed)-210.6(vaccines)-215.2(for)]TJ 0 -1.142 TD [(human)-390.6(papillomavirus.)]TJ /F11 1 Tf 9.7999 0 TD [(Hum)-395(Vaccin)-396(Immunother)]TJ /F8 1 Tf 10.5451 0 TD [(.)-397.5(\(2014\))-394.7(10:3446)]TJ /F12 1 Tf 6.7061 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(54.)-387.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.4583 0 TD (10.4161/)Tj -31.0197 -1.142 TD (hv.34408)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(130.)-499.4(Einstein)-212.4(MH,)-210.4(Levin)-215.7(MJ,)-211.1(Chatterjee)-210.7(A,)-212.7(Chakhtoura)-206(N,)-209.3(Takacs)-215.4(P,)-208.1(Catteau)-210.2(G,)-216(et)-205.3(al.)]TJ -0.9233 -1.142 TD 0.0555 Tc 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[(139.)-499.4(Strauss)-258.7(J,)-261.8(Floudas)-258.3(CS,)-261.7(Sater)-256.5(HA,)-262.6(Manu)-257.4(M,)-257.7(Lamping)-255.8(E,)-264.8(Francis)-256.7(DC,)-259.8(et)-253.9(al.)-261.3(Phase)]TJ -0.9314 -1.142 TD [(II)-411.2(evalsuation)-406.5(of)-407.7(the)-411.3(triple)-406.9(combination)-414.2(of)-407.7(PDS0101,)-407.7(M9241,)-415.1(and)-405.3(bintrafusp)-412.3(alfa)-407.3(in)]TJ T* [(patients)-219.2(with)-222.4(HPV)-224.5(16)-216.4(positive)-224.5(Malignancies.)]TJ /F11 1 Tf 17.7857 0 TD [(J)-214.4(Clin)-222.1(Oncol)]TJ /F8 1 Tf 4.7299 0 TD [(.)-219.4(\(2021\))-216.6(39:2501.)-221.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.5122 0 TD (10.1200/)Tj -31.0278 -1.142 TD (JCO.2021.39.15_suppl.2501)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(140.)-499.4(Dion)-464.6(GR,)-460.5(Teng)-457.5(S,)-464.1(Boyd)-457.9(LR,)-467.4(Northam)-461.8(A,)-463.8(Mason-Apps)-465.1(C,)-454.3(Vieira)-465.5(D,)-462.3(et)-464.5(al.)]TJ -0.9314 -1.142 TD [(Adjuvant)-383.3(human)-390.6(papillomavirus)-381.7(vaccination)-388.8(for)-383.9(secondary)-390(prevention:)-388.4(a)-381(systematic)]TJ T* 0.0247 Tc [(review)5.2(.)]TJ /F11 1 Tf 3.4907 0 TD 0.025 Tc [(JA)8.8(MA)-517.7(Otol)4.8(ary)8.4(n)-2.8(gol)-513.5(H)2.7(ead)-519.8(N)1.2(eck)-519.4(S)-2.9(u)5.3(r)0.2(g)]TJ /F8 1 Tf 15.688 0 TD 0.0233 Tc [(.)-520(\()1.8(2017\))-524.6(143:6)8.3(1)0.2(4)]TJ /F12 1 Tf 7.273 0 TD 0 Tc ()Tj /F8 1 Tf 0.5345 0 TD 0.0236 Tc [(22.)-519.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.8795 0 TD 0.0234 Tc (10.1001/)Tj -30.8658 -1.142 TD 0 Tc (jamaoto.2016.4736)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(141.)-499.4(Di)-250.2(Donato)-246.9(V,)-243.2(Caruso)-252.9(G,)-248.4(Petrillo)-246.6(M,)-249.6(Kontopantelis)-248.7(E,)-248.6(Palaia)-249.3(I,)-250.8(Perniola)-249.9(G,)-240.3(et)-253.9(al.)]TJ -0.9314 -1.142 TD [(A)-9.5(d)0(j)-15.6(u)0(v)-18.2(a)0(n)-10.1(t)-516(H)-9.4(P)0(V)-522.8(v)0(a)-12.1(c)-13.3(ci)-12.4(n)-9.7(a)0(t)-14.2(i)0(o)-17.5(n)-511.9(to)-526.3(pr)-15(ev)-16.9(en)-14.9(t)-516(r)0(e)-13.7(c)0(u)-19.7(rre)-22.3(n)-9.7(t)-507.9(c)-13.3(e)0(r)-13.7(v)-11.8(ic)-12.4(al)-519.8(d)-14.5(y)0(s)-12.2(p)0(l)-15.6(a)0(s)-17(i)0(a)-517.9(a)0(f)-17.1(t)-13.9(er)-515.9(su)-23.1(rg)-12.2(ic)-12.4(al)]TJ T* 0.0551 Tc [(treatm)-7.6(ent:)-553(a)-560.8(m)0.5(et)-7.4(a-analy)-5.2(s)-2.1(is.)]TJ /F11 1 Tf 13.2664 0 TD [(Va)-6.5(ccin)-5(e)-3.4(s)-551.3(\()-0.6(B)-4.5(a)1.6(sel)-5.5(\))]TJ /F8 1 Tf 7.516 0 TD 0.0559 Tc [(.)-560.3(\()2(2021\))-556.8(9:410.)-560.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 9.8485 0 TD 0.0557 Tc (10.3390/)Tj -30.6309 -1.1501 TD 0 Tc (vaccines9050410)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(142.)-499.4(M)26.5(a)32(t)26.6(s)31.9(u)26(z)27.2(a)23.9(k)27.4(i)-331.2(H)31.1(,)-332.7(M)26.5(a)32(k)27.3(i)25.1(y)28.7(a)32(m)26.4(a)-332.4(K)26.2(,)-332.7(H)31.1(a)23.9(s)31.9(e)27.2(g)28.7(a)23.9(w)29.1(a)-332.4(H)31.1(,)-332.7(A)22.9(s)31.9(a)23.9(i)-331.2(R)30.9(,)-332.7(M)26.5(o)30.3(r)23.8(i)33.2(t)26.6(a)-332.4(M)26.5(,)-332.7(O)26.3(s)31.9(h)28.9(i)25.1(m)26.4(a)-332.4(T)30.9(.)-332.7(H)23(u)34(m)26.4(a)23.9(n)]TJ -0.9314 -1.142 TD -0.031 Tc [(p)-5(a)1(p)-5(i)-5.9(llo)-8.8(ma)-7.1(vi)-5.9(ru)-5(s)-306.8(v)-2.3(acci)-5.9(na)-7.1(ti)-5.9(on)-308(as)-306.8(a)-7.1(n)-299.9(a)-7.1(d)-5(ju)-5(van)-8.3(t)-304(t)-4.4(h)-2.1(era)-7.1(p)3.1(y)-310(f)0.8(o)-8.8(r)-298.7(r)-7.2(ecu)-5(rren)-8.3(t)-304(res)-7.2(p)-5(ir)-7.2(at)-4.4(or)-7.2(y)-301.9(p)-5.1(ap)-5(i)-5.9(llo)-8.8(ma)-7.1(t)-4.4(o)-0.7(si)-5.9(s:)]TJ T* [(ad)-5.1(d)-5.1(i)-6(ti)-6(on)-8.4(al)-299.4(ca)-7.2(se)-303.5(s)-7.3(e)-3.9(ri)-6(es.)]TJ /F11 1 Tf 8.3745 0 TD 0.2711 Tc [(JV)297.3(o)301.7(i)298.1(c)297.8(e)]TJ /F8 1 Tf 2.616 0 TD -0.0335 Tc [(.)-309.5(\()1.7(2)-8.1(0)-8(21)-8.1(\))-306(3)-8.1(8:)-9.9(20)-8.1(4)]TJ /F12 1 Tf 5.6694 0 TD 0 Tc ()Tj /F8 1 Tf 0.4778 0 TD -0.0262 Tc [(9.)-294.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 2.6241 0 TD [(10.)5.6(10)7.4(16/j)5.2(.)-2.5(j)5.2(v)2.6(oice.)5.6(202)7.4(1.)5.6(07.)5.6(01)7.5(9)]TJ 0.13725 0.12157 0.12549 scn -18.8305 -1.5712 TD 0 Tc [(143.)-499.4(Hoc)]TJ /F15 1 Tf 3.8228 0.0405 TD ()Tj /F8 1 Tf 0.0081 -0.0405 TD (evar-Boltez)Tj /F15 1 Tf 4.4869 0.0405 TD ()Tj /F8 1 Tf 0.0162 -0.0405 TD [(ar)-349.1(I,)-348(Matic)]TJ /F15 1 Tf 4.3411 0.0405 TD ()Tj /F8 1 Tf 0.0081 -0.0405 TD (ic)Tj /F15 1 Tf 0.6641 0.0405 TD ()Tj /F8 1 Tf 0.3564 -0.0405 TD [(M,)-354.9(S)]TJ /F15 1 Tf 1.879 0.2511 TD ()Tj /F8 1 Tf 0.0486 -0.2511 TD [(ereg-Bahar)-345.7(M,)-354.9(Gale)-343.4(N,)-355.1(Poljak)-346.8(M,)-346.8(Kocjan)-348.7(B,)]TJ -16.5627 -1.142 TD [(et)-432.1(al.)-423.3(Human)-437(papilloma)-428.1(virus)-431.4(vaccination)-437.4(in)-430.1(patients)-429.8(with)-424.9(an)-431.3(aggressive)-435.3(course)-432.9(of)]TJ T* [(recurrent)-314.3(respiratory)-308.1(papillomatosis.)]TJ /F11 1 Tf 14.9753 0 TD [(Eur)-310.5(Arch)-306.1(Otorhinolaryngol)]TJ /F8 1 Tf 10.7718 0 TD [(.)-308.4(\(2014\))-305.7(271:3255)]TJ /F12 1 Tf 7.0057 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (62.)Tj -33.2631 -1.142 TD (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1007/s00405-014-3143-y)Tj 0.13725 0.12157 0.12549 scn -0.8666 -1.5712 TD [(144.)-499.4(Schif)62.7(fman)-284(MH,)-275.2(Bauer)-279.9(HM,)-275.2(Hoover)-282.2(RN,)-275.6(Glass)-282.5(AG,)-274.1(Cadell)-281.5(DM,)-281.9(Rush)-271.2(BB,)-284.5(et)-278.2(al.)]TJ -0.9314 -1.142 TD [(Epidemiologic)-445.8(evidence)-444.7(showing)-443.3(that)-436.6(human)-439.2(papillomavirus)-446.5(infection)-449.8(causes)-439.3(most)]TJ T* [(cervical)-360.4(intraepithelial)-358.4(neoplasia.)]TJ /F11 1 Tf 13.5903 0 TD [(J)-352.1(Natl)-362.6(Cancer)-355.4(Inst)]TJ /F8 1 Tf 7.3864 0 TD [(.)-357(\(1993\))-354.3(85:958)]TJ /F12 1 Tf 6.1472 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(64.)-362.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.3935 0 TD (10.1093/)Tj -31.0278 -1.1501 TD (jnci/85.12.958)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(145.)-499.4(Yang)-223(X,)-222.3(Cheng)-224.7(Y,)-226.1(Li)-221.4(C.)-227.5(The)-228.9(role)-219.4(of)-221.4(TLRs)-225.8(in)-227.6(cervical)-222.7(cancer)-228.6(with)-222.4(HPV)-232.6(infection:)]TJ -0.9314 -1.142 TD 0.5916 Tc [(ar)550.6(e)546(v)547.5(i)543.8(e)545.9(w)547.8(.)]TJ /F11 1 Tf 4.6975 0 TD 0.0451 Tc [(Signal)-542(Transduct)-543.8(T)-1.7(arget)-543.8(T)6.4(her)]TJ /F8 1 Tf 6.9999 0 0 6.9999 177.6755 383.3574 Tm 0.047 Tc [(.)-536.8(\()1.2(201)7.7(7\))-541.4(2\(1)7.7(\))1.2(:e1)7.7(705)7.7(5.)-544.9(doi)7.3(:)]TJ 0.15294 0.15294 0.15294 scn 12.416 0 TD 0.0477 Tc [(10)8.4(.10)8.4(38/)]TJ -30.7119 -1.142 TD 0 Tc (sigtrans.2017.55)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(146.)-499.4(Bansal)-279.5(N,)-274.1(Wright)-275.7(JD,)-278(Cohen)-271.7(CJ,)-278.1(Herzog)-277.1(TJ.)-279.6(Natural)-279.8(history)-274.4(of)-278.1(established)-272.8(low)]TJ -0.9314 -1.142 TD [(grade)-299.6(cervical)-303.7(intraepithelial)-309.8(\(CIN)-302.1(1\))-303.8(lesions.)]TJ /F11 1 Tf 18.385 0 TD [(Anticancer)-304.3(Res)]TJ /F8 1 Tf 5.9124 0 TD [(.)-300.3(\(2008\))-305.7(28:1763)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (6.)Tj -30.396 -1.5712 TD [(147.)-499.4(Chan)-467.3(J,)-464.3(Monk)-460.2(B,)-462.5(Brewer)-468.3(C,)-462.4(Keefe)-467.8(K,)-468.6(Osann)-463.8(K,)-460.5(McMeekin)-470.6(S,)-464.1(et)-464.5(al.)-463.8(HPV)]TJ -0.9314 -1.142 TD 0.0396 Tc [(in)5.6(fectio)5.1(n)-537.1(a)-1.2(n)5.6(d)-541.9(n)5.6(u)0.8(mb)5.1(e)-6(r)-535.9(o)5.1(f)-536(l)6.1(i)-0.1(fetime)-532.5(sex)5.5(u)0.8(al)-536.5(pa)6.8(rtner)6.7(s)-535.9(are)-532.5(s)-1.4(tr)6.7(on)5.6(g)-539.1(p)0.8(r)6.7(e)-6.1(d)8.9(i)-0.1(ctor)6.7(s)-535.9(f)-1.5(o)5.1(r)]TJ /F12 1 Tf T* 0 Tc ()Tj /F8 1 Tf 0.2187 0 TD (natural)Tj /F12 1 Tf 2.8509 0 TD ()Tj /F8 1 Tf 0.2187 0 TD [(regression)-496.7(of)-480.6(CIN)-491.2(2)-484.8(and)-486.3(3.)]TJ /F11 1 Tf 12.1649 0 TD [(Br)-489.5(J)-481.7(Cancer)]TJ /F8 1 Tf 5.0053 0 TD [(.)-486.6(\(2003\))-483.8(89:1062)]TJ /F12 1 Tf 6.8843 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(6.)-485.5(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.1749 0 TD (10.1038/)Tj -31.0278 -1.142 TD (sj.bjc.6601196)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(148.)-499.4(Kang)-319.7(W,)-328.6(Choi)-320.8(H,)-326(Kim)-319.2(S.)-326.4(Is)-323.5(vaccination)-324(with)-327.7(quadrivalent)-330.6(HPV)-321.7(vaccine)-328.1(after)]TJ -0.9314 -1.142 TD 0.0291 Tc [(LEEP)-526.6(ef)60.9(fective)-526.8(i)5.6(n)-531.4(p)-1.6(revent)7.1(ing)-533.4(r)4.3(ecurrenc)]TJ 17.405 0 TD 0.0258 Tc [(e)-530.1(i)-5.8(n)-526.6(p)-4.9(a)-7(t)-4.3(ie)-3.7(nt)-4.3(s)-533.5(w)-1.8(i)-5.8(t)3.8(h)-536.6(h)-2(ig)-10.3(h-gra)-7(d)-4.9(e)-530.1(c)-3.6(e)-3.7(r)1(vi)-5.8(c)-3.7(a)1.1(l)]TJ -17.405 -1.1501 TD 0 Tc [(intraepithelial)-455.6(neoplasia)-446.1(\(CIN2)]TJ /F12 1 Tf 12.7237 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (3\).)Tj /F11 1 Tf 1.4902 0 TD [(Gynecol)-449.8(Oncol)]TJ /F8 1 Tf 5.8881 0 TD [(.)-446.1(\(2013\))-451.4(130:264)]TJ /F12 1 Tf 6.8114 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(8.)-445(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.0939 0 TD (10.1016/)Tj -31.0278 -1.142 TD (j.ygyno.2013.04.050)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(149.)-499.4(Uddin)-256.7(MN,)-255.7(Kouzi)-262.2(SA,)-255(Hussain)-261(MD.)-249.5(Strategies)-262.7(for)-254.3(developing)-261.4(oral)-255.1(vaccines)-263.8(for)]TJ -0.9314 -1.142 TD [(human)-398.7(papillomavirus)-406(\(HPV\))-397(induced)-403.1(cancer)-398.6(using)-400.2(nanoparticle)-402.1(mediated)-399.1(delivery)]TJ T* (system.)Tj /F11 1 Tf 3.2397 0 TD [(J)-295.4(Pharm)-308.8(Pharm)-300.7(Sci)]TJ /F8 1 Tf 7.7104 0 TD [(.)-300.3(\(2015\))-305.7(18:220)]TJ /F12 1 Tf 6.0339 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(34.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.18433/J3RS3V)Tj 0.13725 0.12157 0.12549 scn -19.8429 -1.5712 TD [(150.)-499.4(Kim)-416.4(MG,)-408.2(Park)-415.8(JY,)-414.4(Shon)-414.1(Y,)-412.4(Kim)-416.4(G,)-410.4(Shim)-415.5(G,)-410.4(Oh)-414.6(YK.)-410.5(Nanotechnology)-416.9(and)]TJ -0.9314 -1.142 TD 0.0539 Tc [(vacci)6.1(n)-4.4(e)-550.6(d)-1.1(evelo)-4.9(p)-1.1(m)7.4(e)0.2(nt.)]TJ /F11 1 Tf 10.4398 0 TD 0.0491 Tc [(As)-6.7(i)-4.9(a)-4.5(n)-553.8(J)-562.2(Ph)-7.8(arm)-562.9(S)-3.1(c)-5.2(i)]TJ /F8 1 Tf 8.7957 0 TD 0.0559 Tc [(.)-552.2(\()2(2)8.5(014)8.5(\))-556.8(9)8.5(:22)8.5(7)]TJ /F12 1 Tf 6.698 0 TD 0 Tc ()Tj /F8 1 Tf 0.5669 0 TD 0.0491 Tc [(35)-6.4(.)-559(d)-5.9(oi)-6.8(:)]TJ 0.15294 0.15294 0.15294 scn 4.1468 0 TD 0.0555 Tc [(10.)6.2(1016)8.1(/)]TJ -30.6471 -1.142 TD 0 Tc (j.ajps.2014.06.002)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(151.)-499.4(Karimi)-432.6(H,)-431.3(Soleimanjahi)-442.7(H,)-431.3(Abdoli)-433.6(A,)-431.4(Banijamali)-438.7(RS.)-433.2(Combination)-433.4(therapy)]TJ -0.9314 -1.142 TD [(using)-278.7(human)-269.1(papillomavirus)-284.5(L1/E6/E7)-273.2(genes)-275.3(and)-275.7(archaeosome:)-274.7(A)-276.8(nanovaccine)-277.3(confer)]TJ T* 0.032 Tc [(immuneadj)6.6(u)1.3(va)7.3(nting)-522.4(e)-5.6(f)63.8(f)7.1(ects)-527.3(to)]TJ /F9 1 Tf 13.7118 0 TD 0 Tc ()Tj /F8 1 Tf 0.5588 0 TD 0.0309 Tc [(g)-5.1(h)3.1(t)-525.6(c)-6.7(ervical)-529(c)1.4(anc)-6.6(e)1.4(r.)]TJ /F11 1 Tf 9.2654 0 TD 0.0276 Tc [(Sci)-536.6(R)-3(ep)]TJ /F8 1 Tf 3.2801 0 TD 0.0314 Tc [(.)-536.2(\()1.8(202)8.3(0)0.2(\))-532.7(10:57)8.2(87.)]TJ -26.8162 -1.142 TD 0 Tc (doi:)Tj 0.15294 0.15294 0.15294 scn 1.798 0 TD (10.1038/s41598)Tj /F12 1 Tf 6.1796 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (020-62448)Tj /F12 1 Tf 4.1873 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (3)Tj 0.13725 0.12157 0.12549 scn -12.254 -1.5712 TD [(152.)-499.4(Rupar)-355.5(MJ,)-364.9(Golusinski)-360.6(P,)-353.9(Golusinski)-360.6(W,)-361(Masternak)-365.4(M.)-354.9(Radiotherapy.)-359.8(human)]TJ -0.9314 -1.1501 TD [(pap)-13.3(ill)-9.4(oma)-16.6(vir)-11.4(us)-509.1(an)-10.1(d)-508.6(the)-508.5(us)-15(e)-507.3(o)0(f)-504.9(n)-9.7(an)-10.1(opart)-15.2(ic)-12.4(les)-508.9(fo)-10.8(r)-510.7(imm)-11.2(uno)-10.3(th)-9.3(erap)-12.5(y)-505.8(i)0(n)-511.1(H)-9.4(PV-r)-15.4(ela)-14.7(ted)]TJ 0 -1.142 TD 0.0212 Tc [(cancer:)-522.1(a)-521.8(rev)-6.7(i)5.8(ew)-6.4(.)]TJ /F11 1 Tf 7.9371 0 TD 0.0221 Tc [(Rep)-519.4(P)-0.9(r)5.4(a)0.9(ct)-518.2(Oncol)-516.4(R)-0.4(adiother)]TJ /F8 1 Tf 11.7923 0 TD 0.0231 Tc [(.)-520.2(\()1.6(2)8.1(019\))-516.7(24:)6.2(544)]TJ /F12 1 Tf 6.7466 0 TD 0 Tc ()Tj /F8 1 Tf 0.5345 0 TD 0.0237 Tc [(50.)-511.5(doi)8.3(:)]TJ 0.15294 0.15294 0.15294 scn 3.8633 0 TD 0.0234 Tc [(10.1)8.4(0)0.2(16/)]TJ -30.8739 -1.142 TD 0 Tc (j.rpor.2019.08.006)Tj 0.13725 0.12157 0.12549 scn 0.9314 -1.5712 TD [(153.)-499.4(Idrees)-470.4(H,)-463.7(Zaidi)-465.1(SZJ,)-472.4(Sabir)-465.6(A,)-463.8(Khan)-473.5(RU,)-463.8(Zhang)-469.1(X,)-465.3(Hassan)-466.3(S.)-472.2(A)-463.1(review)-470.5(of)]TJ -0.9314 -1.142 TD [(biodegradabl)-13.5(e)-499.2(natural)-502.1(polymer-b)-13.4(ased)-498.4(nanopar)-13.1(ticles)-502.8(for)-505.3(drug)-503(delivery)-502.7(applications.)]TJ /F11 1 Tf T* [(Nanomaterials)-308.5(\(Basel\))]TJ /F8 1 Tf 8.8443 0 TD [(.)-300.3(\(2020\))-297.6(10:1970.)-302.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.8362 0 TD (10.3390/nano10101970)Tj 0.13725 0.12157 0.12549 scn -16.749 -1.5712 TD [(154.)-499.4(Gohar)-505.3(A,)-504.3(Ali)-503.8(AA,)-505.7(Elkhati)-11.9(b)-496.2(WF,)-505.1(El-S)-10.2(ayyad)-508.6(GS,)-501.2(Elfadil)-507.7(D,)-502.8(Nored)-12.3(din)-501.3(AM.)]TJ -0.9314 -1.142 TD [(Combination)-441.5(therapy)-438.5(between)-441.5(prophylactic)-436.4(and)-445.8(therapeutic)-440.4(human)-439.2(papillomavirus)]TJ T* [(\(HPV\))-291.7(vaccines)-296.2(with)-295.3(special)-293.3(emphasis)-297.1(on)-287.3(implementation)-296.8(of)-294.3(nanotechnology.)]TJ /F11 1 Tf 31.6109 0 TD (Microb)Tj -31.6109 -1.142 TD (Pathog)Tj /F8 1 Tf 2.7375 0 TD [(.)-300.3(\(2022\))-305.7(171:105747.)-298.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 10.2778 0 TD (10.1016/j.micpath.2022.105747)Tj 0.13725 0.12157 0.12549 scn 24.3784 94.282 TD [(155.)-499.4(Witeof)-227.4(AE,)-225.8(Meinerz)-225.2(NM,)-231.4(Walker)-226.6(KD,)-225.5(Funke)-219.2(HH,)-230.1(Garcea)-226.9(RL,)-224.5(Randolph)-225.8(TW.)-224.8(A)]TJ -0.9233 -1.142 TD [(single)-383.8(dose,)-387.5(thermostable,)-387.1(trivalent)-387.6(human)-382.5(papillomavirus)-389.8(vaccine)-384.8(formulated)-390.9(using)]TJ T* 0.0554 Tc [(a)6.5(t)1(o)4.7(m)0.8(ic)-557.2(l)5.7(a)-1.6(yer)-552.5(d)0.4(epo)4.7(s)-1.8(itio)4.7(n.)]TJ /F11 1 Tf 11.9057 0 TD 0.6032 Tc [(JP)547.8(h)546.3(a)549.6(r)554.1(m)-8.8(S)551(c)548.9(i)]TJ /F8 1 Tf 5.7018 0 TD 0.0556 Tc [(.)-552.5(\()1.7(202)8.2(3\))-557.1(11)8.2(2:22)8.2(23)]TJ /F12 1 Tf 8.3097 0 TD 0 Tc ()Tj /F8 1 Tf 0.5669 0 TD 0.0474 Tc [(29)-8.1(.)-560.7(d)-7.7(o)-11.4(i)-0.4(:)]TJ 0.15294 0.15294 0.15294 scn 4.1549 0 TD 0.0559 Tc [(10.1)8.5(0)0.4(16/)]TJ -30.639 -1.142 TD 0 Tc (j.xphs.2023.02.007)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(156.)-499.4(Wahid)-296.9(R,)-301.9(Cannon)-291(MJ,)-300.1(Chow)-292.6(M.)-298.2(Virus-speci)]TJ /F9 1 Tf 20.1263 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(c)-296.7(CD4+)-293.5(and)-291.9(CD8+)-301.6(cytotoxic)-290(T-)]TJ -21.5842 -1.142 TD [(cell)-296(responses)-306(and)-308.1(long-term)-303.7(T-cell)-299.9(memory)-307(in)-300.5(individuals)-307.6(vaccinated)-308.3(against)-303(polio.)]TJ /F11 1 Tf 34.1216 0 TD (J)Tj -34.1216 -1.142 TD (Virol)Tj /F8 1 Tf 2.0086 0 TD [(.)-300.3(\(2005\))-297.6(79:5988)]TJ /F12 1 Tf 6.5117 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(95.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.1128/JVI.79.10.5988)Tj /F12 1 Tf 9.2573 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (5995.2005)Tj 0.13725 0.12157 0.12549 scn -21.1549 -1.5712 TD [(15)-13.9(7.)-517.9(Pu)-11.4(g)-11.7(l)-9.2(ie)-12.4(se)-13.7(-)-10.5(G)0(a)-13.2(r)0(c)-13.7(i)0(a)-526(M)0(,)-516.9(H)-9.4(ey)-16.9(er)-13.7(da)-14.9(hl)-523(LW)-15.6(,)-510.9(M)0(w)-17.4(a)0(m)-14.5(b)0(a)-520.9(C)0(,)-519.1(N)-14.2(kwe)-21.7(mu)-522.7(S,)-520.8(Ch)-11.7(il)-16.4(en)-14.9(gi)-521.2(R)-9.6(,)]TJ -0.9233 -1.1501 TD [(Dem)-11.1(o)-10.2(lis)-519.1(R)-9.6(,)-510.9(et)-513.1(al)-17.6(.)-510.9(Fac)-12(to)-16(rs)-519.3(in)]TJ /F9 1 Tf 12.1487 0 TD ()Tj /F8 1 Tf 6.9999 0 0 6.9999 393.6755 690.3495 Tm [(ue)-11.6(n)-9.7(c)0(i)-12.4(n)0(g)-515.6(v)0(a)-12.1(c)0(c)-10.3(i)0(n)-17(e)-507.3(ac)-13.6(ce)-10.3(pt)-12.2(an)-18.2(ce)-512.5(an)-10.1(d)-516.7(hes)-17.3(it)-13(an)-10.1(cy)-519.1(in)-511.1(th)-17.4(re)-13.7(e)]TJ -12.6832 -1.142 TD [(informal)-424.6(settlements)-423.2(in)-422(Lusaka,)-430(Zambia.)]TJ /F11 1 Tf 17.1216 0 TD (Vaccine)Tj /F8 1 Tf 3.102 0 TD [(.)-421.8(\(2018\))-427.1(36:5617)]TJ /F12 1 Tf 6.7628 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(24.)-427.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.5231 0 TD (10.1016/)Tj -31.0197 -1.142 TD (j.vaccine.2018.07.042)Tj 0.13725 0.12157 0.12549 scn 0.9233 -1.5712 TD [(158.)-499.4(Uddin)-386.2(MN,)-385.3(Henry)-384.8(B,)-381.5(Carter)-384.9(KD,)-379.4(Roni)-385.2(MA,)-380.6(Kouzi)-383.7(SS.)-384.9(A)-382.1(novel)-386.3(formulation)]TJ -0.9233 -1.142 TD [(strategy)-308.8(to)-299.5(deliver)-312.7(combined)-311.4(DNA)-307.2(and)-300(VLP)-307.7(based)-314.3(HPV)-305.5(vaccine.)]TJ /F11 1 Tf 26.4923 0 TD [(J)-303.5(Pharm)-308.8(Pharm)-308.8(Sci)]TJ /F8 1 Tf 7.7266 0 TD (.)Tj -34.2188 -1.142 TD [(\(2019\))-297.6(22:536)]TJ /F12 1 Tf 5.5155 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(47.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.18433/jpps30768)Tj 0.13725 0.12157 0.12549 scn -8.3826 -1.5712 TD [(159.)-499.4(He)-273.8(M,)-273.9(Zhu)-275.5(L,)-271.5(Yang)-271.6(N,)-274.1(Li)-270(H,)-277.4(Yang)-271.6(Q.)-274.1(Recent)-275.6(advances)-274.4(of)-270(oral)]TJ /F9 1 Tf 27.0997 0 TD ()Tj /F8 1 Tf 0.5265 0 TD [(lm)-274.4(as)-268.1(platform)]TJ -28.5494 -1.142 TD [(for)-278.6(drug)-276.2(delivery.)]TJ /F11 1 Tf 7.2163 0 TD [(Int)-283.8(J)-279.2(Pharm)]TJ /F8 1 Tf 4.738 0 TD [(.)-284.1(\(2021\))-281.4(604:120759.)-282.7(doi:)]TJ 0.15294 0.15294 0.15294 scn 10.1887 0 TD (10.1016/j.ijpharm.2021.120759)Tj 0.13725 0.12157 0.12549 scn -21.2197 -1.5712 TD [(160.)-499.4(Jacob)-408.7(S,)-399.3(Nair)-403(AB,)-407.2(Boddu)-402.3(SH,)-400.6(Gorain)-405.4(B,)-405.8(Sreeharsha)-410.1(N,)-395.6(Shah)-406.1(J.)-407.6(An)-400(updated)]TJ -0.9233 -1.142 TD [(ove)-11(rv)-12.2(ie)-12.4(w)-513.6(o)0(f)-513(t)0(h)-9.3(e)-515.4(em)-11.2(er)-13.7(gi)-10.9(ng)-515.6(ro)-10.7(l)-9.2(e)-507.3(o)-10.2(f)-510.8(pat)-12.6(ch)-519(an)-10.1(d)]TJ /F9 1 Tf 19.5837 0 TD ()Tj /F8 1 Tf 0.5345 0 TD [(l)-9.2(m-b)-10.6(as)-17(ed)-513.8(b)-10.2(u)0(c)-11.6(cal)-516.8(de)-11.6(l)-9.2(i)0(v)-10.9(e)0(r)-13.7(y)-505.8(sy)-12.2(st)-14.3(em)-11.2(s.)]TJ /F11 1 Tf -20.1182 -1.142 TD (Pharmaceutics)Tj /F8 1 Tf 5.7666 0 TD [(.)-300.3(\(2021\))-305.7(13:1206.)-302.3(doi:)]TJ 0.15294 0.15294 0.15294 scn 8.8361 0 TD (10.3390/pharmaceutics13081206)Tj 0.13725 0.12157 0.12549 scn -13.6794 -1.5712 TD [(161.)-499.4(Barnabas)-289.5(RV,)-285.2(Brown)-291.2(ER,)-282.6(Onono)-289.1(MA,)-283.4(Bukusi)-293.1(EA,)-282.4(Njoroge)-288.1(B,)-284.3(Winer)-293.9(RL,)-281.2(et)-286.3(al.)]TJ -0.9233 -1.1501 TD (Ef)Tj /F9 1 Tf 0.8018 0 TD ()Tj /F8 1 Tf 0.5426 0 TD [(ca)-13.6(cy)-519.1(o)-10.2(f)-518.9(si)-15.8(ng)-13.4(l)-9.2(e)0(-)-15.6(dos)-17.2(e)-515.4(h)-11.6(um)-12.5(an)-528.5(pa)-14.9(pi)-13.7(l)-9.2(l)-9.2(o)0(m)-16.3(a)0(v)-12.1(i)0(r)-15.8(u)0(s)-525.3(v)0(a)-12.1(c)-13.3(ci)-12.4(n)-9.7(a)0(t)-14.2(i)0(o)-17.5(n)-511.9(am)-14.5(o)-10.2(n)-9.7(g)-513.9(y)0(o)-13.9(u)0(n)-16.2(g)-513.9(A)-9.5(f)0(r)-17.2(i)0(c)-12.4(a)0(n)]TJ -1.3445 -1.142 TD (women.)Tj /F11 1 Tf 3.4664 0 TD [(NEJM)-301.6(Evid)]TJ /F8 1 Tf 4.495 0 TD [(.)-300.3(\(2022\))-305.7(1:EVIDoa2100056.)-298(doi:)]TJ 0.15294 0.15294 0.15294 scn 13.0558 0 TD (10.1056/EVIDoa2100056)Tj 0.13725 0.12157 0.12549 scn -20.0939 -1.5712 TD [(162.)-499.4(Brotherton)-221.7(JM,)-211.1(Budd)-213.9(A,)-212.7(Rompotis)-218.2(C,)-211.3(Bartlett)-210.8(N,)-217.4(Malloy)-208.6(MJ,)-219.2(Andersen)-216.9(RL,)-208.3(et)-213.4(al.)]TJ -0.9233 -1.142 TD [(Is)-315.4(one)-324.8(dose)-322(of)-326.7(human)-325.8(papillomavirus)-325(vaccine)-328.1(as)-316.7(ef)59.1(fective)-324.3(as)-324.8(three?:)-326.1(a)-324.3(national)-320(cohort)]TJ T* (analysis.)Tj /F11 1 Tf 3.6284 0 TD [(Papillomavirus)-311.7(Res)]TJ /F8 1 Tf 7.5727 0 TD [(.)-300.3(\(2019\))-305.7(8:100177.)-301.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 9.314 0 TD (10.1016/j.pvr.2019.100177)Tj 0.13725 0.12157 0.12549 scn -19.5918 -1.5712 TD [(163.)-499.4(Watson-Jones)-238.7(D,)-235.5(Changalucha)-228.8(J,)-237.5(Whitworth)-230.2(H,)-228.8(Pinto)-232.4(L,)-231(Mutani)-238(P,)-232.4(Indangasi)-231.6(J,)]TJ -0.9233 -1.142 TD [(et)-221.5(al.)-228.9(Immunogenicity)-231.1(and)-227.1(safety)-234.7(of)-229.5(one-dose)-228.1(human)-228.6(papillomavirus)-227.8(vaccine)-230.9(compared)]TJ T* [(with)-295.3(two)-294.7(or)-302.3(three)-295.5(doses)-298.2(in)-300.5(Tanzanian)-303.5(girls)-296.4(\(DoRIS\):)-307.3(an)-293.6(open-label,)-303.7(randomised,)-304.5(non-)]TJ T* [(inferiority)-390(trial.)]TJ /F11 1 Tf 6.6251 0 TD [(Lancet)-381.8(Glob)-388.6(Health)]TJ /F8 1 Tf 7.9371 0 TD [(.)-381.3(\(2022\))-394.7(10:e1473)]TJ /F12 1 Tf 7.1029 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(e84.)-384.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.8633 0 TD (10.1016/S2214)Tj /F12 1 Tf 5.8071 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (109X)Tj -32.356 -1.142 TD (\(22\)00309)Tj /F12 1 Tf 4.0415 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (6)Tj 0.13725 0.12157 0.12549 scn -3.6284 -1.5712 TD [(164.)-499.4(Rodriguez)-297.5(AM,)-299.6(Zeybek)-294.8(B,)-292.4(Vaughn)-290.6(M,)-298.2(Westra)-291.5(J,)-294.2(Kaul)-297.6(S,)-285.9(Montealegre)-303.9(JR,)-287.7(et)-294.4(al.)]TJ -0.9233 -1.1501 TD [(Comparison)-205.3(of)-205.2(the)-208.9(long-term)-206.5(impact)-209.3(and)-210.9(clinical)-207.3(outcomes)-211.6(of)-148.5(fewer)-209.1(doses)-209.1(and)-202.9(standard)]TJ 0 -1.142 TD [(doses)-265.8(of)-261.9(human)-261(papillomavirus)-276.4(vaccine)-263.3(in)-268.1(the)-265.6(United)-261.1(States:)-271.1(a)-259.5(database)-272.2(study.)]TJ /F11 1 Tf 31.4408 0 TD (Cancer)Tj /F8 1 Tf 2.778 0 TD (.)Tj -34.2188 -1.142 TD [(\(2020\))-297.6(126:1656)]TJ /F12 1 Tf 6.4712 0 TD ()Tj /F8 1 Tf 0.5103 0 TD [(67.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2801 0 TD (10.1002/cncr.32700)Tj 0.13725 0.12157 0.12549 scn -9.3383 -1.5712 TD [(165.)-499.4(Basu)-218(P,)-216.2(Malvi)-212.7(SG,)-217.8(Joshi)-217.9(S,)-213(Bhatla)-221.9(N,)-209.3(Muwonge)-222.8(R,)-212.8(Lucas)-218.5(E,)-216.2(et)-213.4(al.)-212.7(Vaccine)-218.7(ef)]TJ /F9 1 Tf 31.2545 0 TD ()Tj /F8 1 Tf 0.5345 0 TD (cacy)Tj -32.7124 -1.142 TD [(against)-294.9(persistent)-306(human)-301.5(papillomavirus)-300.7(\(HPV\))-299.9(16/18)-305.2(infection)-295.9(at)-297.7(10)-305.5(years)-293.6(after)-303.9(one,)]TJ T* [(two,)-408.8(and)-421.5(three)-417(doses)-411.6(of)-415.8(quadrivalent)-419.7(HPV)-418.9(vaccine)-417.2(in)-422(girls)-409.8(in)-422(India:)-412.4(a)-413.4(multicentre,)]TJ T* [(prospective,)-300(cohort)-302.8(study.)]TJ /F11 1 Tf 10.6585 0 TD [(Lancet)-300.9(Oncol)]TJ /F8 1 Tf 5.2401 0 TD [(.)-300.3(\(2021\))-305.7(22:1518)]TJ /F12 1 Tf 6.5198 0 TD ()Tj /F8 1 Tf 0.5102 0 TD [(29.)-306.2(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2802 0 TD (10.1016/S1470)Tj /F12 1 Tf 5.799 0 TD ()Tj /F8 1 Tf 0.5103 0 TD (2045)Tj -32.518 -1.142 TD (\(21\)00453)Tj /F12 1 Tf 4.0415 0 TD ()Tj /F8 1 Tf 0.5102 0 TD (8)Tj 0.13725 0.12157 0.12549 scn -3.6284 -1.5712 TD [(166.)-499.4(Kreimer)-403.4(AR,)-392.4(Sampson)-399.6(JN,)-397.6(Porras)-397.7(C,)-397.6(Schiller)-398.1(JT,)-393(Kemp)-396.5(T,)-399.1(Herrero)-395.9(R,)-399.1(et)-391.6(al.)]TJ -0.9233 -1.142 TD [(evalsuation)-292.9(of)-294.3(durability)-300.2(of)-294.3(a)-300(single)-294.7(dose)-297.7(of)-294.3(the)-298(bivalent)-294.4(HPV)-297.4(vaccine:)-304.5(the)-289.9(CVT)-300.8(trial.)]TJ /F11 1 Tf 34.1216 0 TD (J)Tj -34.1216 -1.142 TD [(Natl)-297.8(Cancer)-298.7(Inst)]TJ /F8 1 Tf 6.6089 0 TD [(.)-300.4(\(2020\))-297.6(112:1038)]TJ /F12 1 Tf 6.9896 0 TD ()Tj /F8 1 Tf 0.5183 0 TD [(46.)-298.1(doi:)]TJ 0.15294 0.15294 0.15294 scn 3.2721 0 TD (10.1093/jnci/djaa011)Tj 0.13725 0.12157 0.12549 scn -16.4655 -1.5712 TD [(167.)-499.4(Di)-282.6(J,)-278(Wang)-276.9(J,)-278(Wang)-276.9(S,)-277.8(Ma)-273.6(M,)-282(Zhang)-274.8(H,)-277.4(Liu)-276.5(N,)-274.1(et)-278.2(al.)-277.5(Self-boosting)-279.3(vaccination)]TJ -0.9233 -1.1501 TD [(ba)-18.7(se)-21.8(d)-516.7(o)-10.2(n)-520(p)-14.5(ul)-15.6(s)-16.7(a)0(t)-14.2(i)-15.4(l)-9.2(e)-515.4(a)-16.6(n)-9.7(ti)-21.1(ge)-16.9(n)-520(r)0(e)-21.8(l)-9.2(e)-13.3(a)0(s)-17(e)-523.5(fr)-17.2(o)-10.2(m)-524.4(c)-13.3(o)-10.2(re)]TJ /F12 1 Tf 19.3245 0 TD ()Tj /F8 1 Tf 0.5264 0 TD [(sh)-20.2(el)-22.4(l)-519.4(m)0(i)-13.3(c)-13.3(r)0(o)-18.8(p)-14.5(ar)-17(t)-13.9(i)0(c)-20.5(l)-9.2(e)-13.3(s)0(.)]TJ /F11 1 Tf 8.9333 0 TD [(S)-11.7(m)-12.7(al)-17.1(l)]TJ /F8 1 Tf 2.2597 0 TD [(.)-519(\()-13.4(20)-22(23)-13.9(\))]TJ -31.044 -1.142 TD [(19:2207892.)-298.9(doi:)]TJ 0.15294 0.15294 0.15294 scn 6.8438 0 TD (10.1002/smll.202207892)Tj 0.13725 0.12157 0.12549 scn -5.9205 -1.5712 TD [(168.)-499.4(Arinaminpathy)-459.1(N,)-452.3(Lavine)-450.9(JS,)-449.9(Grenfell)-449.2(BT.)-447.8(Self-boosting)-457.4(vaccines)-450.1(and)-445.8(their)]TJ -0.9233 -1.142 TD [(imp)-11.7(l)-9.2(ica)-12.8(ti)-13.1(ons)-514.5(fo)-10.8(r)-510.7(her)-17.3(d)-508.6(i)0(m)-13.3(m)0(u)-12.5(nit)-14.7(y.)]TJ /F11 1 Tf 14.2545 0 TD [(Pro)-17.2(c)-507.8(N)0(a)-12.7(t)0(l)-511.9(A)0(c)-13.8(a)0(d)-509.4(S)-11.8(ci)-513.2(U.)-13.5(S.)-9.5(A)]TJ /F8 1 Tf 10.9986 0 TD [(.)-510.9(\()0(2)-12.2(012)-12.8(\))-515.5(109)-12.8(:20)-14.6(15)-13.9(4)]TJ /F12 1 Tf 7.9614 0 TD 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trailer <> startxref 116 %%EOF %BeginExifToolUpdate 1470 0 obj << /Type /Metadata /Subtype /XML /Length 4834 >> stream Rui Wang Hongpeng Huang Chulin Yu Xuefeng Li Yang Wang Liangzhi Xie Wang R, Huang H, Yu C, Li X, Wang Y and Xie L (2024) Current status and future directions for the development of human papillomavirus vaccines. Front. Immunol. 15:1362770 Copyright 漏 2024 Wang, Huang, Yu, Li, Wang and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. human papillomavirus vaccine prophylactic therapeutic antigens adjuvants formulation strategy Current status and future directions for the development of human papillomavirus vaccines human papillomavirus vaccine, prophylactic, therapeutic, antigens, adjuvants, formulation strategy True https://www.frontiersin.org/legal/copyright-statement endstream endobj 842 0 obj << /Keywords (human papillomavirus vaccine, prophylactic, therapeutic, antigens, adjuvants, formulation strategy) >> endobj 844 0 obj << /PageMode /UseOutlines /Names 847 0 R /Outlines 1444 0 R /Pages 838 0 R /OpenAction [ null /Fit ] /Threads 845 0 R /Type /Catalog /PageLabels 836 0 R /Metadata 1470 0 R >> endobj xref 0 1 0000000841 65535 f 841 2 0000000000 00001 f 0001054596 00000 n 844 1 0001054735 00000 n 1470 1 0001049667 00000 n trailer << /Size 1471 /Prev 116 /Root 844 0 R /ID [ <58EC4C73563EFA479E438A8963BD223B> ] /Info 842 0 R >> %EndExifToolUpdate 1049645 startxref 1054940 %%EOF