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Vaccine. 2004 Feb 25;22(8):991-1000.

Immunization of chimpanzees with an envelope protein-based vaccine enhances specific humoral and cellular immune responses that delay hepatitis C virus infection.

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1
Laboratory of Hepatitis Viruses, Division of Viral Products, CBER, FDA, Building 29A, Room 1D02, 8800 Rockville Pike, Bethesda, MD 20892, USA.

Abstract

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.

PMID:
15161076
DOI:
10.1016/j.vaccine.2003.09.010
[Indexed for MEDLINE]
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