Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus(HCV) envelope E2 protein modified the infection after challenge with homologous monoclonal HCV

Hepatitis C virus (HCV) is an important cause of chronic liver disease worl dwide. Development of vaccines to prevent HCV infection, or at least preven t progression to chronicity, is a major goal. In mice and rhesus macaques, a DNA vaccine encoding cell-surface HCV-envelope 2 (E2) glyco-protein stimu lated stronger immune responses than a vaccine encoding intracellular E2. T herefore, we used DNA encoding surface-expressed E2 to immunize chimpanzees 2768 and 3001. Chimpanzee 3001 developed anti-E2 after the second immuniza tion and antibodies to hypervariable region 1 (HVR1) after the third immuni zation. Although chimpanzee 2768 had only low levels of anti-E2 after the t hird immunization, an anamnestic response occurred after HCV challenge. CTL responses to E2 were not detected before challenge, but a strong response was detected after HCV challenge in chimpanzee 2768. An E2-specific CD4+ re sponse was detected in chimpanzee 2768 before challenge and in both chimpan zees postchallenge. Three weeks after the last immunization, animals were c hallenged with 100 50% chimpanzee-infectious doses (CID50) of homologous mo noclonal HCV. As a control, a naive chimpanzee was inoculated with 3 CID50 of the challenge virus. The vaccine did not generate sterilizing immunity b ecause both vaccinated chimpanzees were infected. However, both vaccinated chimpanzees resolved the infection early whereas the control animal became chronically infected. Compared with the control animal, hepatitis appeared earlier in the course of the infection in both vaccinated chimpanzees. Ther efore, DNA vaccine encoding cell surface-expressed E2 did not elicit steril izing immunity in chimpanzees against challenge with a monoclonal homologou s virus, but did appear to modify the infection and might have prevented pr ogression to chronicity.