Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4~+ and CD8~+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

摘要

T cell-mediated immune responses play an important role in the containment of HIV-1 replication. Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8~+ and CD4~+ T cells. The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-euv (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4~+ and CD8~+ T cell responses in both naive and infected macaque. In this study, the immunogenicity of NYVAC-SIV-gpe alone was compared with a combination regimen where priming with an optimized DNA-SIV-gag-env vaccine candidate was followed by a NYVAC-SIV-gpe boost. In macaques immunized with the prime-boost regimen, the extent and durability of CD8~+ T cell response to an immunodominant SIV gag epitope was increased and these animals recognized a broader array of subdominant SIV epitopes in the cytolytic assay. In addition, the prime-boost regimen significantly enhanced the proliferative respeonses to both SIV gag and env proteins. Thus, the combination of these vaccine modalities may represent a valuable strategy in the development of a vaccine for HIV.