Attenuated nef DNA vaccine construct induces cellular immune response: role in HIV-1 multiprotein vaccine

HIV-1 positive patients generate Nef-specific CTL response, indicating that Nef is a potent immunogen. However, Nef is also known to down regulate the expression of CD4 and MHC-I molecules, thereby protecting virally infected target cells. We compared the immunogenicity of non-functional nef vaccine constructs to wild type functional nef as potential immunogen. Mice were immunized with different nef constructs and assessed for their ability to induce cellular immune responses. Evaluation of T cell immune responses in mice showed that non-functional nef vaccine constructs are capable of inducing a significant T cell immune response measured by IFN-γ ELISPOT. Further epitope mapping studies indicate that one of our attenuated constructs, Nef R-38, has multiple CTL epitopes spanning throughout the gene. Our results indicate that functionally attenuated Nef antigen might be a better candidate for future multiprotein HIV-1 vaccine.