Synergistic Effect of Combined HIV/HCV Immunogens: A Combined HIV-1/HCV Candidate Vaccine Induces a Higher Level of CD8+ T Cell-Immune Responses in HLA-A2.1 Mice

Dual infections with HIV-1 and Hepatitis C virus (HCV) may proceed in concert to cause severe disease. HIV positive individuals that become infected with HCV advance more rapidly to AIDS than those that are infected with HIV- 1 alone. In this study, HLA-A2.1 mice were immunized with a combination vaccine including HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine containing either HIV or HCV immunogens. Mice immunized with the combined HIV/HCV regimen had similar antibody titers as the group receiving either the HIV-1 or HCV only regimen. Proliferative immune responses showed that mice receiving the combined HIV/HCV vaccine exhibited a three fold higher stimulation index (SI) to gp120 than mice immunized with the vaccine containing HIV alone. To determine whether our vaccine strategy induced Th1 or Th2 immune responses, IFN-γ and IL-4/IL-5 were measured. The combined HIV/HCV vaccine induced a higher level of Th1 responses to HIV-1 gag protein compared with the other groups, as measured by IFN-γ production. Interestingly, detection of IFN-γ by ELISPOT assay demonstrated that the combined HIV/HCV vaccine group had increased numbers of spot forming cells (SFC) to HIV-gp120 peptides when compared to that of the HIV-1 only vaccine group. The combined HIV/HCV vaccine group also showed an increase in SFC to HCV-core peptides in comparison with the group receiving the HCV only vaccine. Intracellular IFN-γ staining confirmed the ELISPOT results and demonstrated that the combined HIV/HCV group had significantly higher percentages of HIV and HCV-specific CD8+T cells in comparison to the groups receiving the HIV or HCV vaccines. These results suggest a new approach to maximize vaccine efficacy against HIV and HCV.