Immunization of chimpanzees with an envelope protein-based vaccine enhances specific humoral and cellular immune responses that delay hepatitis C virus infection.
Two chimpanzees, one naïve (Ch1601) and one recovered from hepatitis C virus (HCV) acute infection (Ch1587), were vaccinated with recombinant envelope glycoproteins (E1E2) and then challenged with 100 CID50 of HCV. Results of the challenge were compared to infection in a non-vaccinated control animal. Immunization generated high antibody titers to E1E2 including antibody specifically directed to the hypervariable region 1 (HVR1) in addition to strong and specific HVR1 T-cell proliferative responses. Upon challenge with HCV, viremia was delayed 3 weeks in both vaccinated animals compared to the non-immunized (control) animal. Ch1601 HCV RNA titers were maintained below 5 x 10(4) copies/ml, and alanine aminotransferase levels were only minimally elevated. An increase in intrahepatic cytokine mRNA levels coincided with a fall in HCV RNA to non-quantifiable levels. Despite this apparent control of virus replication the animal became persistently infected. Ch1587 had a significantly shorter and milder viremia, compared to the re-infection of the non-vaccinated control animal. This data indicates that a strategy inducing a T-cell immune response combined with antibody responses to E1E2 would make a viable candidate for an HCV vaccine.
Puig
Montserrat
M
Laboratory of Hepatitis Viruses, Division of Viral Products, CBER, FDA, Building 29A, Room 1D02, 8800 Rockville Pike, Bethesda, MD 20892, USA.
Major
Marian E
ME
Mihalik
Kathleen
K
Feinstone
Stephen M
SM
D000818:Animals; D000917:Antibody Formation; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D007111:Immunity, Cellular; D002679:Pan troglodytes; D055502:Secondary Prevention; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D016207:Cytokines; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C114224:envelope protein E1, GB virus C; C107619:glycoprotein E2, GB virus C