Gastroenterology
Volume 139, Issue 3 , Pages 965-974 , September 2010

Meta-Analysis of Hepatitis C Virus Vaccine Efficacy in Chimpanzees Indicates an Importance for Structural Proteins

  • Harel Dahari

      Affiliations

    • Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
  • ,
  • Stephen M. Feinstone

      Affiliations

    • Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
  • ,
  • Marian E. Major

      Affiliations

    • Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
    • Corresponding Author InformationReprint requests Address requests for reprints to: Marian E. Major, PhD, Laboratory of Hepatitis Viruses, Division of Viral Products, Building 29A/Rm 1D10/HFM 448, 8800 Rockville Pike, Bethesda, Maryland 20892. fax: (301) 496-1810

Received 12 February 2010 ,Accepted 26 May 2010.

References 

  1. Bartenschlager R, Frese M, Pietschmann T. Novel insights into hepatitis C virus replication and persistence. Adv Virus Res. 2004;63:71–180
  2. Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol. 2007;5:453–463
  3. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–562
  4. Liang TJ, Rehermann B, Seeff LB, et al. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000;132:296–305
  5. National Institutes of Health Consensus Development Conference statement: management of hepatitis C: 2002. June 10–12, 2002. Hepatology. 2002;36:S3–S20
  6. Stumpf MP, Pybus OG. Genetic diversity and models of viral evolution for the hepatitis C virus. FEMS Microbiol Lett. 2002;214:143–152
  7. Duffy S, Shackelton LA, Holmes EC. Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet. 2008;9:267–276
  8. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy. Science. 1998;282:103–107
  9. Simmonds P, Bukh J, Combet C, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42:962–973
  10. Murphy D, Chamberland J, Dandavino R, et al. A new genotype of hepatitis C virus originating from central Africa. Hepatology. 2007;46:623A
  11. Erickson AL, Kimura Y, Igarashi S, et al. The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity. 2001;15:883–895
  12. Bowen DG, Walker CM. Mutational escape from CD8+ T-cell immunity: HCV evolution, from chimpanzees to man. J Exp Med. 2005;201:1709–1714
  13. Uebelhoer L, Han JH, Callendret B, et al. Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness. PLoS Pathog. 2008;4:1–15
  14. Weiner AJ, Geysen HM, Christopherson C, et al. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. Proc Natl Acad Sci U S A. 1992;89:3468–3472
  15. 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;68:1494–1500
  16. 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;132:667–678
  17. Grakoui A, Shoukry NH, Woollard DJ, et al. HCV persistence and immune evasion in the absence of memory T cell help. Science. 2003;302:659–662
  18. Major ME, Mihalik K, Puig M, et al. Previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis C virus replication upon rechallenge. J Virol. 2002;76:6586–6595
  19. Nascimbeni M, Mizukoshi E, Bosmann M, et al. Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees. J Virol. 2003;77:4781–4793
  20. 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;197:1645–1655
  21. 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;99:15661–15668
  22. Puig M, Mihalik K, Yu MY, et al. Sensitivity and reproducibility of HCV quantitation in chimpanzee sera using TaqMan real-time PCR assay. J Virol Methods. 2002;105:253–263
  23. Engle RE, Russell RS, Purcell RH, et al. Development of a TaqMan assay for the six major genotypes of hepatitis C virus: comparison with commercial assays. J Med Virol. 2008;80:72–79
  24. Forns X, Thimme R, Govindarajan S, et al. Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees. Proc Natl Acad Sci U S A. 2000;97:13318–13323
  25. Lindenbach BD, Meuleman P, Ploss A, et al. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A. 2006;103:3805–3809
  26. Wakita T, Pietschmann T, Kato T, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005;11:791–796
  27. Youn JW, Park SH, Lavillette D, et al. Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee. Hepatology. 2005;42:1429–1436
  28. 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;82:10896–10905
  29. 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;39:1709–1720
  30. Woollard DJ, Grakoui A, Shoukry NH, et al. Characterization of HCV-specific Patr class II restricted CD4+ T cell responses in an acutely infected chimpanzee. Hepatology. 2003;38:1297–1306
  31. 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;12:190–197
  32. Rollier C, Depla E, Drexhage JA, et al. Control of heterologous hepatitis C virus infection in chimpanzees is associated with the quality of vaccine-induced peripheral T-helper immune response. J Virol. 2004;78:187–196
  33. 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;32:618–625
  34. 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;104:8427–8432
  35. Bukh J, Apgar CL, Engle R, et al. Experimental infection of chimpanzees with hepatitis C virus of genotype 5a: genetic analysis of the virus and generation of a standardized challenge pool. J Infect Dis. 1998;178:1193–1197
  36. Hong Z, Beaudet-Miller M, Lanford RE, et al. Generation of transmissible hepatitis C virions from a molecular clone in chimpanzees. Virology. 1999;256:36–44
  37. Yanagi M, St Claire M, Shapiro M, et al. Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. Virology. 1998;244:161–172
  38. Sakai A, Takikawa S, Thimme R, et al. In vivo study of the HC-TN strain of hepatitis C virus recovered from a patient with fulminant hepatitis: RNA transcripts of a molecular clone (pHC-TN) are infectious in chimpanzees but not in Huh7.5 cells. J Virol. 2007;81:7208–7219
  39. Meunier JC, Engle RE, Faulk K, et al. Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1. Proc Natl Acad Sci U S A. 2005;102:4560–4565
  40. Kato T, Choi Y, Elmowalid G, et al. Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation. Hepatology. 2008;48:732–740
  41. Kamili S, Krawczynski K, McCaustland K, et al. Infectivity of hepatitis C virus in plasma after drying and storing at room temperature. Infect Control Hosp Epidemiol. 2007;28:519–524
  42. Prince AM, Pawlotsky JM, Soulier A, et al. Hepatitis C virus replication kinetics in chimpanzees with self-limited and chronic infections. J Viral Hepat. 2004;11:236–242
  43. Katayama K, Kumagai J, Komiya Y, et al. Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission. Intervirology. 2004;47:57–64
  44. Shata MT, Tricoche N, Perkus M, et al. Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees. Virology. 2003;314:601–616
  45. Thomson M, Nascimbeni M, Havert MB, et al. The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity. J Virol. 2003;77:862–870
  46. Thomson M, Nascimbeni M, Gonzales S, et al. Emergence of a distinct pattern of viral mutations in chimpanzees infected with a homogeneous inoculum of hepatitis C virus. Gastroenterology. 2001;121:1226–1233
  47. Bukh J, Pietschmann T, Lohmann V, et al. Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proc Natl Acad Sci U S A. 2002;99:14416–14421
  48. Bassett SE, Guerra B, Brasky K, et al. Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection. Hepatology. 2001;33:1479–1487
  49. Bukh J, Thimme R, Meunier JC, et al. Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain. J Virol. 2008;82:8183–8195
  50. Lanford RE, Guerra B, Chavez D, et al. Cross-genotype immunity to hepatitis C virus. J Virol. 2004;78:1575–1581
  51. Prince AM, Brotman B, Lee DH, et al. Protection against chronic hepatitis C virus infection after rechallenge with homologous, but not heterologous, genotypes in a chimpanzee model. J Infect Dis. 2005;192:1701–1709
  52. Coates S, Choo QL, Kuo G, et al. Protection of chimpanzees against Heterologous 1a viral challenge using a gpE1/gpE2 heterodimer vaccine. In:  Jilbert AR,  Grgacic E,  Vickery K, et al. editor. Proceedings of the 11th International Symposium on Viral Hepatitis and Liver Disease. Australian Center for Hepatitis; 2004;p. 118–123Virology
  53. 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;91:1294–1298
  54. Esumi M, Rikihisa T, Nishimura S, et al. Experimental vaccine activities of recombinant E1 and E2 glycoproteins and hypervariable region 1 peptides of hepatitis C virus in chimpanzees. Arch Virol. 1999;144:973–980
  55. Dahari H, Major M, Zhang X, et al. Mathematical modeling of primary hepatitis C infection: noncytolytic clearance and early blockage of virion production. Gastroenterology. 2005;128:1056–1066
  56. Mehta SH, Cox A, Hoover DR, et al. Protection against persistence of hepatitis C. Lancet. 2002;359:1478–1483
  57. Osburn WO, Fisher BE, Dowd KA, et al. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection. Gastroenterology. 2009;138:315–324
  58. Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature. 2005;436:946–952
  59. Duerst RJ, Morrison LA. Innate immunity to herpes simplex virus type 2. Viral Immunol. 2003;16:475–490
  60. Forthal DN, Landucci G, Haubrich R, et al. Antibody-dependent cellular cytotoxicity independently predicts survival in severely immunocompromised human immunodeficiency virus-infected patients. J Infect Dis. 1999;180:1338–1341
  61. Karnasuta C, Paris RM, Cox JH, et al. Antibody-dependent cell-mediated cytotoxic responses in participants enrolled in a phase I/II ALVAC-HIV/AIDSVAX B/E prime-boost HIV-1 vaccine trial in Thailand. Vaccine. 2005;23:2522–2529
  62. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209–2220
  63. Puig M, Mihalik K, Tilton JC, et al. CD4+ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus. Hepatology. 2006;44:736–745
  64. Zubkova I, Choi YH, Chang E, et al. T-cell vaccines that elicit effective immune responses against HCV in chimpanzees may create greater immune pressure for viral mutation. Vaccine. 2009;27:2594–2602
  65. Dahari H, Layden-Almer JE, Kallwitz E, et al. A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease. Gastroenterology. 2009;136:1402–1409
  66. Alter HJ, Seeff LB. Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Semin Liver Dis. 2000;20:17–35
  67. Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36:S35–S46
  68. Corey KE, Mendez-Navarro J, Gorospe EC, et al. Early treatment improves outcomes in acute hepatitis C virus infection: a meta-analysis. J Viral Hepat. 2010;17:201–207
  69. Major ME, Mihalik K, Fernandez J, et al. Long-term follow-up of chimpanzees inoculated with the first infectious clone for hepatitis C virus. J Virol. 1999;73:3317–3325
  70. 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;45:602–613
  71. Puig M, Major ME, Mihalik K, et al. Immunization of chimpanzees with an envelope protein-based vaccine enhances specific humoral and cellular immune responses that delay hepatitis C virus infection. Vaccine. 2004;22:991–1000

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by intramural funds from the Food and Drug Administration, by NIH grant number P20RR18754, and by the University of Illinois Walter Payton Liver Center GUILD (to H.D.).

PII: S0016-5085(10)00839-5

doi: 10.1053/j.gastro.2010.05.077

Gastroenterology
Volume 139, Issue 3 , Pages 965-974 , September 2010