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Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee
Author(s) -
Youn JinWon,
Park SuHyung,
Lavillette Dimitri,
Cosset FrancoisLoic,
Yang SeHwan,
Lee Chang Geun,
Jin HyunTak,
Kim ChangMin,
Shata Mohamed Tarek M.,
Lee DongHun,
Pfahler Wolfram,
Prince Alfred M.,
Sung Young Chul
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20934
Subject(s) - virology , viremia , antibody , immunology , hepatitis c virus , viral load , neutralizing antibody , virus , immune system , vaccination , biology , immunization , medicine , ns3 , immunity
Immune correlates of protection against hepatitis C virus (HCV) infection are not well understood. Here we investigated 2 naive and 6 immunized chimpanzees before and after intravenous challenge, 12 weeks after the last immunization, with 100 50% chimpanzee infectious doses (CID 50 ) of heterologous genotype 1b HCV. Vaccination with recombinant DNA and adenovirus vaccines expressing HCV core, E1E2, and NS3‐5 genes induced long‐term HCV‐specific antibody and T‐cell responses and reduced peak viral load about 100 times compared with controls (5.91 ± 0.38 vs. 3.81 ± 0.71 logs, respectively). There was a statistically significant inverse correlation between peak viral loads and envelope glycoprotein 2 (E2)‐specific antibody responses at the time of challenge. Interestingly, one vaccinee that had sterilizing immunity against slightly heterologous virus generated the highest level of E2‐specific total and neutralizing antibody responses as well as strong NS3/NS5‐specific T‐cell proliferative responses. The other four vaccinees with low levels of E2‐specific antibody had about 44‐fold reduced peak viral loads but eventually developed persistent infections. In conclusion , vaccine‐induced E2‐specific antibody plays an important role in prevention from nonhomologous virus infection and may provide new insight into the development of an effective HCV vaccine. (H EPATOLOGY 2005;42:1429–1436.)