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Review

Hepatitis C virus vaccine candidates inducing protective neutralizing antibodies

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Pages 1535-1544 | Received 22 Mar 2016, Accepted 24 May 2016, Published online: 13 Jun 2016

References

  • Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol. 2013;10(9):553–562.
  • Liang TJ. Current progress in development of hepatitis C virus vaccines. Nat Med. 2013;19(7):869–878.
  • Holz L, Rehermann B. T cell responses in hepatitis C virus infection: historical overview and goals for future research. Antiviral Res. 2015;114:96–105.
  • Baumert TF, Fauvelle C, Chen DY, et al. A prophylactic hepatitis C virus vaccine: a distant peak still worth climbing. J Hepatol. 2014;61(1 Suppl):S34–44.
  • Lauer GM. Immune responses to hepatitis C virus (HCV) infection and the prospects for an effective HCV vaccine or immunotherapies. J Infect Dis. 2013;207(Suppl 1):S7–S12.
  • Feinstone SM, Hu DJ, Major ME. Prospects for prophylactic and therapeutic vaccines against hepatitis C virus. Clin Infect Dis. 2012;55(Suppl 1):S25–S32.
  • Halliday J, Klenerman P, Barnes E. Vaccination for hepatitis C virus: closing in on an evasive target. Expert Rev Vaccines. 2011;10(5):659–672.
  • Chung RT, Baumert TF. Curing chronic hepatitis C–the arc of a medical triumph. N Engl J Med. 2014;370(17):1576–1578.
  • Cox AL. MEDICINE. Global control of hepatitis C virus. Science. 2015;349(6250):790–791.
  • Callaway E. Hepatitis C drugs not reaching poor. Nature. 2014;508(7496):295–296.
  • Liang TJ, Ghany MG. Therapy of hepatitis C–back to the future. N Engl J Med. 2014;370(21):2043–2047.
  • Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016. published online 18 February 2016. doi:10.1016/S1473-3099(16)00052-9.
  • Van Der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584–2593.
  • Midgard H, Bjoro B, Maeland A, et al. Hepatitis C reinfection after sustained virological response. J Hepatol. 2016;64(5):1020–1026.
  • Hahn JA, Wylie D, Dill J, et al. Potential impact of vaccination on the hepatitis C virus epidemic in injection drug users. Epidemics. 2009;1(1):47–57.
  • Scott N, McBryde E, Vickerman P, et al. The role of a hepatitis C virus vaccine: modelling the benefits alongside direct-acting antiviral treatments. BMC Med. 2015;13:198.
  • Krahn MD, John-Baptiste A, Yi Q, et al. Potential cost-effectiveness of a preventive hepatitis C vaccine in high risk and average risk populations in Canada. Vaccine. 2005;23(13):1549–1558.
  • Honegger JR, Zhou Y, Walker CM. Will there be a vaccine to prevent HCV infection? Semin Liver Dis. 2014;34(1):79–88.
  • Van Damme P, Ward J, Shouval D, et al. Hepatitis B vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. London: Elsevier; 2013. p. 205–234.
  • Vidor E, Plotkin SA. Poliovirus vaccine—inactivated. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. London: Elsevier; 2013. p. 573–597.
  • Schiller JT, Lowy DR, Markowitz LE. Human papillomavirus vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. London: Elsevier; 2013. p. 235–256.
  • Ball JK, Tarr AW, McKeating JA. The past, present and future of neutralizing antibodies for hepatitis C virus. Antiviral Res. 2014;105:100–111.
  • Zeisel MB, Felmlee DJ, Baumert TF. Hepatitis C virus entry. Curr Top Microbiol Immunol. 2013;369:87–112.
  • Nabel GJ. Designing tomorrow’s vaccines. N Engl J Med. 2013;368(6):551–560.
  • Ndongo N, Berthillon P, Pradat P, et al. Association of anti-E1E2 antibodies with spontaneous recovery or sustained viral response to therapy in patients infected with hepatitis C virus. Hepatology. 2010;52(5):1531–1542.
  • Petit M-A, Jolivet-Reynaud C, Peronnet E, et al. Mapping of a conformational epitope shared between E1 and E2 on the serum-derived human hepatitis C virus envelope. J Biol Chem. 2003;278(45):44385–44392.
  • Choo QL, Kuo G, Ralston R, et al. Vaccination of chimpanzees against infection by the hepatitis C virus. Proc Natl Acad Sci U S A. 1994;91(4):1294–1298.
  • Meunier J-C, Gottwein JM, Houghton M, et al. Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus. J Infect Dis. 2011;204(8):1186–1190.
  • Forns X, Payette PJ, Ma X, et al. Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus (HCV) envelope E2 protein modified the infection after challenge with homologous monoclonal HCV. Hepatology. 2000;32(3):618–625.
  • Elmowalid GA, Qiao M, Jeong S-H, et al. Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. Proc Natl Acad Sci U S A. 2007;104(20):8427–8432.
  • Leroux-Roels G, Depla E, Hulstaert F, et al. A candidate vaccine based on the hepatitis C E1 protein: tolerability and immunogenicity in healthy volunteers. Vaccine. 2004;22(23–24):3080–3086.
  • Frey SE, Houghton M, Coates S, et al. Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine. 2010;28(38):6367–6373.
  • Stamataki Z, Coates S, Abrignani S, et al. Immunization of human volunteers with hepatitis C virus envelope glycoproteins elicits antibodies that cross-neutralize heterologous virus strains. J Infect Dis. 2011;204(5):811–813.
  • Law JL, Chen C, Wong J, et al. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PLoS One. 2013;8(3):e59776.
  • Alvarez-Lajonchere L, Shoukry NH, Gra B, et al. Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial. J Viral Hepat. 2009;16(3):156–167.
  • Colombatto P, Brunetto MR, Maina AM, et al. HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNalpha2a and Ribavirin: a randomized controlled trial. J Viral Hepat. 2014;21(7):458–465.
  • Kong L, Giang E, Nieusma T, et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science. 2013;342(6162):1090–1094.
  • Khan AG, Whidby J, Miller MT, et al. Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2. Nature. 2014;509(7500):381–384.
  • Scarselli E, Ansuini H, Cerino R, et al. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. Embo J. 2002;21(19):5017–5025.
  • Pileri P, Uematsu Y, Campagnoli S, et al. Binding of hepatitis C virus to CD81. Science. 1998;282(5390):938–941.
  • Douam F, Dao Thi VL, Maurin G, et al. Critical interaction between E1 and E2 glycoproteins determines binding and fusion properties of hepatitis C virus during cell entry. Hepatology. 2014;59(3):776–788.
  • Farci P, Alter HJ, Wong DC, et al. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci U S A. 1994;91(16):7792–7796.
  • Shimizu YK, Hijikata M, Iwamoto A, et al. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol. 1994;68(3):1494–1500.
  • von Hahn T, Yoon JC, Alter H, et al. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology. 2007;132(2):667–678.
  • Bankwitz D, Steinmann E, Bitzegeio J, et al. Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. J Virol. 2010;84(11):5751–5763.
  • Prentoe J, Jensen TB, Meuleman P, et al. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization. J Virol. 2011;85(5):2224–2234.
  • Keck Z-Y, Girard-Blanc C, Wang W, et al. Antibody response to the hypervariable region-1 interferes with broadly neutralizing antibodies to hepatitis C virus. J Virol. 2016;90(6):3112–3122.
  • Giang E, Dorner M, Prentoe JC, et al. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc Natl Acad Sci U S A. 2012;109(16):6205–6210.
  • Keck Z-Y, Op De Beeck A, Hadlock KG, et al. Hepatitis C virus E2 has three immunogenic domains containing conformational epitopes with distinct properties and biological functions. J Virol. 2004;78(17):9224–9232.
  • Keck Z-Y, Li T-K, Xia J, et al. Analysis of a highly flexible conformational immunogenic domain a in hepatitis C virus E2. J Virol. 2005;79(21):13199–13208.
  • Keck ZY, Xia J, Wang Y, et al. Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate. PLoS Pathog. 2012;8(4):e1002653.
  • Law M, Maruyama T, Lewis J, et al. Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med. 2008;14(1):25–27.
  • Flint M, Maidens C, Loomis-Price LD, et al. Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J Virol. 1999;73(8):6235–6244.
  • Sabo MC, Luca VC, Prentoe J, et al. Neutralizing monoclonal antibodies against hepatitis C virus E2 protein bind discontinuous epitopes and inhibit infection at a postattachment step. J Virol. 2011;85(14):7005–7019.
  • Owsianka A, Tarr AW, Juttla VS, et al. Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein. J Virol. 2005;79(17):11095–11104.
  • Broering TJ, Garrity KA, Boatright NK, et al. Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus. J Virol. 2009;83(23):12473–12482.
  • Mancini N, Diotti RA, Perotti M, et al. Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes. PLoS One. 2009;4(12):e8254.
  • Alhammad Y, Gu J, Boo I, et al. Monoclonal antibodies directed toward the hepatitis C virus glycoprotein E2 detect antigenic differences modulated by the N-terminal hypervariable region 1 (HVR1), HVR2, and intergenotypic variable region. J Virol. 2015;89(24):12245–12261.
  • Keck Z-Y, Li T-K, Xia J, et al. Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies. J Virol. 2008;82(12):6061–6066.
  • Owsianka AM, Timms JM, Tarr AW, et al. Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J Virol. 2006;80(17):8695–8704.
  • Krey T, Meola A, Keck ZY, et al. Structural basis of HCV neutralization by human monoclonal antibodies resistant to viral neutralization escape. PLoS Pathog. 2013;9(5):e1003364.
  • Kaufmann KW, Lemmon GH, Deluca SL, et al. Practically useful: what the Rosetta protein modeling suite can do for you. Biochemistry. 2010;49(14):2987–2998.
  • Kong L, Giang E, Robbins JB, et al. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1. Proc Natl Acad Sci U S A. 2012;109(24):9499–9504.
  • Bohne-Lang A, Von Der Lieth C-W. GlyProt: in silico glycosylation of proteins. Nucleic Acids Res. 2005;33:W214–219.
  • Keck Z-Y, Li SH, Xia J, et al. Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity. J Virol. 2009;83(12):6149–6160.
  • Chung RT, Gordon FD, Curry MP, et al. Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study. Am J Transplant. 2013;13(4):1047–1054.
  • Pantua H, Diao J, Ultsch M, et al. Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies. J Mol Biol. 2013;425(11):1899–1914.
  • Dhillon S, Witteveldt J, Gatherer D, et al. Mutations within a conserved region of the hepatitis C virus E2 glycoprotein that influence virus-receptor interactions and sensitivity to neutralizing antibodies. J Virol. 2010;84(11):5494–5507.
  • Keck ZY, Angus AG, Wang W, et al. Non-random escape pathways from a broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412–423. PLoS Pathog. 2014;10(8):e1004297.
  • Tarr AW, Owsianka AM, Jayaraj D, et al. Determination of the human antibody response to the epitope defined by the hepatitis C virus-neutralizing monoclonal antibody AP33. J Gen Virol. 2007;88(Pt 11):2991–3001.
  • Keck Z, Wang W, Wang Y, et al. Cooperativity in virus neutralization by human monoclonal antibodies to two adjacent regions located at the amino terminus of hepatitis C virus E2 glycoprotein. J Virol. 2013;87(1):37–51.
  • Tarr AW, Khera T, Hueging K, et al. Genetic diversity underlying the envelope glycoproteins of hepatitis C virus: structural and functional consequences and the implications for vaccine design. Viruses. 2015;7(7):3995–4046.
  • Fafi-Kremer S, Fofana I, Soulier E, et al. Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J Exp Med. 2010;207(9):2019–2031.
  • Fauvelle C, Felmlee DJ, Baumert TF. Unraveling hepatitis C virus structure. Cell Res. 2014;24(4):385–386.
  • Dowd KA, Netski DM, Wang X-H, et al. Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. Gastroenterology. 2009;136(7):2377–2386.
  • Farci P, Shimoda A, Coiana A, et al. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science. 2000;288(5464):339–344.
  • Prentoe J, Verhoye L, Velazquez Moctezuma R, et al. HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice. Gut. 2015. published online 20 November 2015. doi:10.1136/gutjnl-2015-310300.
  • Helle F, Goffard A, Morel V, et al. The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein. J Virol. 2007;81(15):8101–8111.
  • Helle F, Vieyres G, Elkrief L, et al. Role of N-linked glycans in the functions of hepatitis C virus envelope proteins incorporated into infectious virions. J Virol. 2010;84(22):11905–11915.
  • Falkowska E, Kajumo F, Garcia E, et al. Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. J Virol. 2007;81(15):8072–8079.
  • Brimacombe CL, Grove J, Meredith LW, et al. Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J Virol. 2011;85(1):596–605.
  • Timpe JM, Stamataki Z, Jennings A, et al. Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology. 2008;47(1):17–24.
  • Xiao F, Fofana I, Heydmann L, et al. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents. PLoS Pathog. 2014;10(5):e1004128.
  • Fofana I, Xiao F, Thumann C, et al. A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits hepatitis C virus cell-cell transmission. PLoS One. 2013;8(5):e64221.
  • Mailly L, Xiao F, Lupberger J, et al. Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nat Biotechnol. 2015;33(5):549–554.
  • Meuleman P, Catanese MT, Verhoye L, et al. A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo. Hepatology. 2012;55(2):364–372.
  • Fofana I, Fafi-Kremer S, Carolla P, et al. Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies. Gastroenterology. 2012;143(1):223–233.
  • Grove J, Nielsen S, Zhong J, et al. Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies. J Virol. 2008;82(24):12020–12029.
  • Andre P, Komurian-Pradel F, Deforges S, et al. Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol. 2002;76(14):6919–6928.
  • Fauvelle C, Felmlee DJ, Crouchet E, et al. Apolipoprotein E mediates evasion from hepatitis C virus neutralizing antibodies. Gastroenterology. 2016;150(1):206–217.
  • Bartosch B, Dubuisson J, Cosset F-L. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med. 2003;197(5):633–642.
  • Pestka JM, Zeisel MB, Blaser E, et al. Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proc Natl Acad Sci U S A. 2007;104(14):6025–6030.
  • Osburn WO, Snider AE, Wells BL, et al. Clearance of hepatitis C infection is associated with the early appearance of broad neutralizing antibody responses. Hepatology. 2014;59(6):2140–2151.
  • Raghuraman S, Park H, Osburn WO, et al. Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. J Infect Dis. 2012;205(5):763–771.
  • Féray C, Gigou M, Samuel D, et al. Incidence of hepatitis C in patients receiving different preparations of hepatitis B immunoglobulins after liver transplantation. Ann Intern Med. 1998;128(10):810–816.
  • Osburn WO, Fisher BE, Dowd KA, et al. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection. Gastroenterology. 2010;138(1):315–324.
  • Park S-H, Shin E-C, Capone S, et al. Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus. Gastroenterology. 2012;143(4):1048–1060.
  • Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J Clin Invest. 2009;119(7):1745–1754.
  • Thimme R, Oldach D, Chang KM, et al. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 2001;194(10):1395–1406.
  • Thimme R, Bukh J, Spangenberg HC, et al. Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci U S A. 2002;99(24):15661–15668.
  • Urbani S, Amadei B, Fisicaro P, et al. Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses. Hepatology. 2006;44(1):126–139.
  • Raziorrouh B, Sacher K, Tawar RG, et al. Virus-specific CD4+ T cells have functional and phenotypic characteristics of follicular T-helper cells in patients with acute and chronic HCV infections. Gastroenterology. 2016;150(3):696–706.
  • Houghton M. Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses. Immunol Rev. 2011;239(1):99–108.
  • Wong JA, Bhat R, Hockman D, et al. Recombinant hepatitis C virus envelope glycoprotein vaccine elicits antibodies targeting multiple epitopes on the envelope glycoproteins associated with broad cross-neutralization. J Virol. 2014;88(24):14278–14288.
  • Verstrepen BE, Depla E, Rollier CS, et al. Clearance of genotype 1b hepatitis C virus in chimpanzees in the presence of vaccine-induced E1-neutralizing antibodies. J Infect Dis. 2011;204(6):837–844.
  • Baumert TF, Ito S, Wong DT, et al. Hepatitis C virus structural proteins assemble into viruslike particles in insect cells. J Virol. 1998;72(5):3827–3836.
  • Lechmann M, Murata K, Satoi J, et al. Hepatitis C virus-like particles induce virus-specific humoral and cellular immune responses in mice. Hepatology. 2001;34(2):417–423.
  • Jeong SH, Qiao M, Nascimbeni M, et al. Immunization with hepatitis C virus-like particles induces humoral and cellular immune responses in nonhuman primates. J Virol. 2004;78(13):6995–7003.
  • El-Awady MK, Tabll AA, Yousif H, et al. Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus. Vaccine. 2010;28(52):8338–8344.
  • Garrone P, Fluckiger AC, Mangeot PE, et al. A prime-boost strategy using virus-like particles pseudotyped for HCV proteins triggers broadly neutralizing antibodies in macaques. Sci Transl Med. 2011;3(94):94ra71.
  • Akazawa D, Moriyama M, Yokokawa H, et al. Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice. Gastroenterology. 2013;145(2):447–455.
  • Youn J-W, Park S-H, Lavillette D, et al. Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee. Hepatology. 2005;42(6):1429–1436.
  • Patient R, Hourioux C, Vaudin P, et al. Chimeric hepatitis B and C viruses envelope proteins can form subviral particles: implications for the design of new vaccine strategies. N Biotechnol. 2009;25(4):226–234.
  • Beaumont E, Patient R, Hourioux C, et al. Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine. Hepatology. 2013;57(4):1303–1313.
  • Scull MA, Shi C, De Jong YP, et al. Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice. Hepatology. 2015;62(1):57–67.

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