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Review

Current and future prophylactic vaccines for hepatitis C virus

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Pages 31-44 | Published online: 11 Aug 2015

References

  • Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–538.
  • Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006;13(1):34–41.
  • Muhlberger N, Schwarzer R, Lettmeier B, Sroczynski G, Zeuzem S, Siebert U. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health. 2009;9:34.
  • Yeung CY, Lee HC, Chan WT, Jiang CB, Chang SW, Chuang CK. Vertical transmission of hepatitis C virus: current knowledge and perspectives. World J Hepatol. 2014;6(9):643–651.
  • Garfein RS, Vlahov D, Galai N, Doherty MC, Nelson KE. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses. Am J Public Health. 1996;86(5):655–661.
  • van de Laar T, Pybus O, Bruisten S, et al. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology. 2009;136(5):1609–1617.
  • Flamm SL, Parker RA, Chopra S. Risk factors associated with chronic hepatitis C virus infection: limited frequency of an unidentified source of transmission. Am J Gastroenterol. 1998;93(4):597–600.
  • Smith DB, Bukh J, Kuiken C, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318–327.
  • Sievert W, Altraif I, Razavi HA, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 2011;31(Suppl 2):61–80.
  • Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77–87.
  • Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(9286):958–965.
  • Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut. 2006;55(9):1350–1359.
  • Fox AN, Jacobson IM. Recent successes and noteworthy future prospects in the treatment of chronic hepatitis C. Clin Infect Dis. 2012;55(Suppl 1):S16–S24.
  • Kimdo Y, Ahn SH, Han KH. Emerging therapies for hepatitis C. Gut Liver. 2014;8(5):471–479.
  • Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today’s treatment paradigm. J Viral Hepat. 2014;21(Suppl 1):34–59.
  • Welsch C, Jesudian A, Zeuzem S, Jacobson I. New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Gut. 2012;61(Suppl 1):i36–i46.
  • Hill A, Cooke G. Medicine. Hepatitis C can be cured globally, but at what cost? Science. 2014;345(6193):141–142.
  • Vieyres G, Thomas X, Descamps V, Duverlie G, Patel AH, Dubuisson J. Characterization of the envelope glycoproteins associated with infectious hepatitis C virus. J Virol. 2010;84(19):10159–10168.
  • Falkowska E, Kajumo F, Garcia E, Reinus J, Dragic T. Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. J Virol. 2007;81(15):8072–8079.
  • Zhu YZ, Qian XJ, Zhao P, Qi ZT. How hepatitis C virus invades hepatocytes: the mystery of viral entry. World J Gastroenterol. 2014;20(13):3457–3467.
  • Sharma NR, Mateu G, Dreux M, Grakoui A, Cosset FL, Melikyan GB. Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion. J Biol Chem. 2011;286(35):30361–30376.
  • 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.
  • Kong L, Giang E, Nieusma T, et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science. 2013;342(6162):1090–1094.
  • El Omari K, Iourin O, Kadlec J, et al. Unexpected structure for the N-terminal domain of hepatitis C virus envelope glycoprotein E1. Nat Commun. 2014;5:4874. doi: 10.1038/ncomms5874.
  • Courouce AM, Bouchardeau F, Girault A, Le Marrec N. Significance of NS3 and NS5 antigens in screening for HCV antibody. Lancet. 1994;343(8901):853–854.
  • Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 2001;194(10):1395–1406.
  • Netski DM, Mosbruger T, Depla E, et al. Humoral immune response in acute hepatitis C virus infection. Clin Infect Dis. 2005;41(5):667–675.
  • Park SH, Rehermann B. Immune responses to HCV and other hepatitis viruses. Immunity. 2014;40(1):13–24.
  • Cooper S, Erickson AL, Adams EJ, et al. Analysis of a successful immune response against hepatitis C virus. Immunity. 1999;10(4):439–449.
  • Post JJ, Pan Y, Freeman AJ, et al; Hepatitis C Incidence and Transmission in Prisons Study (HITS) Group. Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort. J Infect Dis. 2004;189(10):1846–1855.
  • Razvi S, Schneider L, Jonas MM, Cunningham-Rundles C. Outcome of intravenous immunoglobulin-transmitted hepatitis C virus infection in primary immunodeficiency. Clin Immunol. 2001;101(3):284–288.
  • 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.
  • Bjoro K, Froland SS, Yun Z, Samdal HH, Haaland T. Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. N Engl J Med. 1994;331(24):1607–1611.
  • Ennishi D, Terui Y, Yokoyama M, et al. Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV-infected CD20-positive B-cell lymphoma undergoing rituximab combination chemotherapy. Am J Hematol. 2008;83(1):59–62.
  • Raghuraman S, Park H, Osburn WO, Winkelstein E, Edlin BR, Rehermann B. 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.
  • Dowd KA, Netski DM, Wang XH, Cox AL, Ray SC. Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. Gastroenterology. 2009;136(7):2377–2386.
  • Pestka JM, Zeisel MB, Bläser 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.
  • Farci P, Shimoda A, Wong D, et al. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc Natl Acad Sci U S A. 1996;93(26):15394–15399.
  • Morin TJ, Broering TJ, Leav BA, et al. Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in chimpanzees. PLoS Pathog. 2012;8(8):e1002895.
  • Yu MY, Bartosch B, Zhang P, et al. Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma. Proc Natl Acad Sci U S A. 2004;101(20):7705–7710.
  • Bresee JS, Mast EE, Coleman PJ, et al. Hepatitis C virus infection associated with administration of intravenous immune globulin. A cohort study. JAMA. 1996;276(19):1563–1567.
  • MassBiologics. Open Label Study of the Efficacy and Safety of MBL-HCV1 in Combination With Oral Direct-Acting Antivirals in Patients Undergoing Liver Transplantation for Hepatitis C [Internet]; 2015 [cited January 21, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01532908.
  • Major ME, Dahari H, Mihalik K, et al. Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees. Hepatology. 2004;39(6):1709–1720.
  • 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.
  • Dustin LB, Rice CM. Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol. 2007;25:71–99.
  • Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med. 2013;19(7):859–868.
  • Day CL, Lauer GM, Robbins GK, et al. Broad specificity of virus-specific CD4+ T-helper-cell responses in resolved hepatitis C virus infection. J Virol. 2002;76(24):12584–12595.
  • Dustin LB, Cashman SB, Laidlaw SM. Immune control and failure in HCV infection – tipping the balance. J Leukoc Biol. 2014;96(4):535–548.
  • Callendret B, Walker C. A siege of hepatitis: immune boost for viral hepatitis. Nat Med. 2011;17(3):252–253.
  • Day CL, Seth NP, Lucas M, et al. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J Clin Invest. 2003;112(6):831–842.
  • Gerlach JT, Diepolder HM, Jung MC, et al. Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology. 1999;117(4):933–941.
  • Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492–499.
  • Grakoui A, Shoukry NH, Woollard DJ, et al. HCV persistence and immune evasion in the absence of memory T cell help. Science. 2003;302(5645):659–662.
  • Shoukry NH, Grakoui A, Houghton M, et al. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med. 2003;197(12):1645–1655.
  • Watanabe H, Wells F, Major ME. Clearance of hepatitis C in chimpanzees is associated with intrahepatic T-cell perforin expression during the late acute phase. J Viral Hepat. 2010;17(4):245–253.
  • Grebely J, Page K, Sacks-Davis R, et al; InC3 Study Group. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59(1):109–120.
  • Ribeiro RM, Li H, Wang S, et al. Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog. 2012;8(8):e1002881.
  • 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.
  • Helle F, Duverlie G, Dubuisson J. The hepatitis C virus glycan shield and evasion of the humoral immune response. Viruses. 2011;3(10):1909–1932.
  • 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.
  • 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.
  • 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.
  • Dreux M, Pietschmann T, Granier C, et al. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem. 2006;281(27):18285–18295.
  • Bartosch B, Verney G, Dreux M, et al. An interplay between hypervariable region 1 of the hepatitis C virus E2 glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes both enhancement of infection and protection against neutralizing antibodies. J Virol. 2005;79(13):8217–8229.
  • Voisset C, Op de Beeck A, Horellou P, et al. High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry. J Gen Virol. 2006;87(pt 9):2577–2581.
  • Sautto G, Tarr AW, Mancini N, Clementi M. Structural and antigenic definition of hepatitis C virus E2 glycoprotein epitopes targeted by monoclonal antibodies. Clin Dev Immunol. 2013;2013:450963.
  • Burton DR, Ahmed R, Barouch DH, et al. A blueprint for HIV vaccine discovery. Cell Host Microbe. 2012;12(4):396–407.
  • Ahmed FK, Clark BE, Burton DR, Pantophlet R. An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Vaccine. 2012;30(5):922–930.
  • Kwong PD, Mascola JR, Nabel GJ. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol. 2013;13:693–701.
  • Wang S, Mata-Fink J, Kriegsman B, et al. Manipulating the selection forces during affinity maturation to generate cross-reactive HIV antibodies. Cell. 2015;160(4):785–797.
  • He L, Zhu J. Computational tools for epitope vaccine design and evaluation. Curr Opin Virol. 2015;11:103–112.
  • 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.
  • Dahari H, Feinstone SM, Major ME. Meta-analysis of hepatitis C virus vaccine efficacy in chimpanzees indicates an importance for structural proteins. Gastroenterology. 2010;139(3):965–974.
  • 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.
  • 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.
  • Beaumont E, Patient R, Hourioux C, Dimier-Poisson I, Roingeard P. 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.
  • McCaffrey K, Boo I, Poumbourios P, Drummer HE. Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding. J Virol. 2007;81(17):9584–9590.
  • McCaffrey K, Gouklani H, Boo I, Poumbourios P, Drummer HE. The variable regions of hepatitis C virus glycoprotein E2 have an essential structural role in glycoprotein assembly and virion infectivity. J Gen Virol. 2011;92(pt 1):112–121.
  • 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.
  • 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.
  • Roohvand F, Kossari N. Advances in hepatitis C virus vaccines, part two: advances in hepatitis C virus vaccine formulations and modalities. Expert Opin Ther Pat. 2012;22(4):391–415.
  • Barnes E, Folgori A, Capone S, et al. Novel adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man. Sci Transl Med. 2012;4(115):115ra1.
  • Swadling L, Capone S, Antrobus RD, et al. A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory. Sci Transl Med. 2014;6(261):261ra153.
  • Akondy RS, Monson ND, Miller JD, et al. The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J Immunol. 2009;183(12):7919–7930.
  • Northfield JW, Loo CP, Barbour JD, et al. Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T(EMRA) cells in early infection are linked to control of HIV-1 viremia and predict the subsequent viral load set point. J Virol. 2007;81(11):5759–5765.
  • National Institute of Allergy and Infectious Diseases. Staged phase I/II hepatitis C prophylactic vaccine. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine (US); 2015 [cited January 6, 2015]. Available from: https://clinicaltrials.gov/show/NCT01436357.
  • ReiThera Srl. Study of a new MVA vaccine for hepatitis C virus. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine (US); 2015 [cited January 15, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01296451.
  • Folgori A, Capone S, Ruggeri L, et al. A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees. Nat Med. 2006;12(2):190–197.
  • Fattori E, Zampaglione I, Arcuri M, et al. Efficient immunization of rhesus macaques with an HCV candidate vaccine by heterologous priming-boosting with novel adenoviral vectors based on different serotypes. Gene Ther. 2006;13(14):1088–1096.
  • Park SH, Shin EC, Capone S, et al. Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus. Gastroenterology. 2012;143(4):1048–60. e4.
  • Klade CS, Wedemeyer H, Berg T, et al. Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41. Gastroenterology. 2008;134(5):1385–1395.
  • Firbas C, Boehm T, Buerger V, et al. Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine. Vaccine. 2010;28(12):2397–2407.
  • Drane D, Maraskovsky E, Gibson R, et al. Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX vaccine: a phase I study in healthy volunteers. Hum Vaccin. 2009;5(3):151–157.
  • Polakos NK, Drane D, Cox J, et al. Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine. J Immunol. 2001;166(5):3589–3598.
  • Chmielewska AM, Naddeo M, Capone S, et al. Combined adenovirus vector and hepatitis C virus envelope protein prime-boost regimen elicits T cell and neutralizing antibody immune responses. J Virol. 2014;88(10):5502–5510.
  • Rollier CS, Paranhos-Baccala G, Verschoor EJ, et al. Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity. Hepatology. 2007;45(3):602–613.
  • Youn JW, Hu YW, Tricoche N, et al. Evidence for protection against chronic hepatitis C virus infection in chimpanzees by immunization with replicating recombinant vaccinia virus. J Virol. 2008;82(21):10896–10905.
  • Elmowalid GA, Qiao M, Jeong SH, 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.
  • Beaumont E, Roingeard P. Prospects for prophylactic hepatitis C vaccines based on virus-like particles. Hum Vaccin Immunother. 2013;9(5):1112–1118.
  • Angus AG, Patel AH. Immunotherapeutic potential of neutralizing antibodies targeting conserved regions of the HCV envelope glycoprotein E2. Fut Microbiol. 2011;6(3):279–294.
  • Drummer HE, Boo I, Maerz AL, Poumbourios P. A conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr motif in hepatitis C virus glycoprotein E2 is a determinant of CD81 binding and viral entry. J Virol. 2006;80(16):7844–7853.
  • 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.
  • Castelli M, Clementi N, Sautto GA, et al. HCV E2 core structures and mAbs: something is still missing. Drug Discov Today. 2014;19(12):1964–1970.
  • 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.
  • Tarr AW, Owsianka AM, Timms JM, et al. Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33. Hepatology. 2006;43(3):592–601.
  • Potter JA, Owsianka AM, Jeffery N, et al. Toward a hepatitis C virus vaccine: the structural basis of hepatitis C virus neutralization by AP33, a broadly neutralizing antibody. J Virol. 2012;86(23):12923–12932.
  • Kong L, Giang E, Nieusma T, et al. Structure of hepatitis C virus envelope glycoprotein E2 antigenic site 412 to 423 in complex with antibody AP33. J Virol. 2012;86(23):13085–13088.
  • Li Y, Pierce BG, Wang Q, et al. Structural basis for penetration of the glycan shield of hepatitis c virus E2 glycoprotein by a broadly neutralizing human antibody. J Biol Chem. 2015;290(16):10117–10125.
  • 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.
  • Meola A, Tarr AW, England P, et al. Structural flexibility of a conserved broadly neutralizing epitope in hepatitis C virus glycoprotein E2. J Virol. 2015;89:2170–2181.
  • 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(11):2991–3001.
  • 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.
  • 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.
  • Deng L, Ma L, Virata-Theimer ML, et al. Discrete conformations of epitope II on the hepatitis C virus E2 protein for antibody-mediated neutralization and nonneutralization. Proc Natl Acad Sci U S A. 2014;111(29):10690–10695.
  • Krey T, Meola A, Keck ZY, Damier-Piolle L, Foung SK, Rey FA. Structural basis of HCV neutralization by human monoclonal antibodies resistant to viral neutralization escape. PLoS Pathog. 2013;9(5):e1003364.
  • Drummer HE, Wilson KA, Poumbourios P. Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81. J Virol. 2002;76(21):11143–11147.
  • Harman C, Zhong L, Ma L, et al. A view of the E2-CD81 interface at the binding site of a neutralizing antibody against hepatitis C virus. J Virol. 2015;89(1):492–501.
  • 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.
  • Owsianka AM, Tarr AW, Keck ZY, et al. Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein. J Gen Virol. 2008;89(3):653–659.
  • 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.
  • 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.
  • 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.
  • Keck ZY, Saha A, Xia J, et al. Mapping a region of hepatitis C virus E2 that is responsible for escape from neutralizing antibodies and a core CD81-binding region that does not tolerate neutralization escape mutations. J Virol. 2011;85(20):10451–10463.
  • Roccasecca R, Ansuini H, Vitelli A, et al. Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and is modulated by a complex interplay between hypervariable regions 1 and 2. J Virol. 2003;77(3):1856–1867.
  • Werkhoven PR, van de Langemheen H, van der Wal S, Kruijtzer JAW, Liskamp RMJ. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold. J Pept Sci. 2014;20(4):235–239.
  • Correia BE, Bates JT, Loomis RJ, et al. Proof of principle for epitope-focused vaccine design. Nature. 2014;507(7491):201–206.
  • Torresi J, Fischer A, Grollo L, Zeng W, Drummer H, Jackson DC. Induction of neutralizing antibody responses to hepatitis C virus with synthetic peptide constructs incorporating both antibody and T-helper epitopes. Immunol Cell Biol. 2007;85(2):169–173.
  • Alfonso M, Díaz A, Hernández AM, et al. An anti-idiotype vaccine elicits a specific response to N-glycolyl sialic acid residues of glycoconjugates in melanoma patients. J Immunol. 2002;168(5):2523–2529.
  • Bendandi M. Idiotype vaccines for lymphoma: proof-of-principles and clinical trial failures. Nat Rev Cancer. 2009;9(9):675–681.
  • Owsianka A, Jeffery N, di Lorenzo C, Patel A.. Towards a hepatitis C vaccine; isolation of an anti-idiotypic antibody that mimics a broadly neutralizing epitope on the E2 glycoprotein. In: 21st International Symposium on Hepatitis C virus and Related Viruses; Banff, Canada; 2014.
  • Pumpens P, Grens E. HBV core particles as a carrier for B cell/T cell epitopes. Intervirology. 2001;44(2–3):98–114.
  • Oliveira GA, Wetzel K, Calvo-Calle JM, et al. Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial. Infect Immun. 2005;73(6):3587–3597.
  • Ibañez LI, Roose K, De Filette M, et al. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A. PLoS One. 2013;8(3):e59081.
  • Sanofi. Safety Study of Recombinant M2e Influenza-A Vaccine in Healthy Adults (FLU-A) [Internet]; 2015 [cited January 6, 2015]. Available from: https://clinicaltrial.gov/show/NCT00819013.
  • Netter HJ, Macnaughton TB, Woo WP, Tindle R, Gowans EJ. Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes. J Virol. 2001;75(5):2130–2141.
  • Vaccari M, Poonam P, Franchini G. Phase III HIV vaccine trial in Thailand: a step toward a protective vaccine for HIV. Expert Rev Vaccines. 2010;9(9):997–1005.
  • Pettersen EF, Goddard TD, Huang CC, et al. UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–1612.