This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.During the reporting period we evaluated how preexisting immunity to vaccinia affects the immunogenicity and efficacy of a DNA/MVA SIV vaccine in macaques. Three groups of macaques, eight per group, were studied. The non-Dryvax group received the DNA/MVA SIV vaccine (DNA at weeks 0 and 8, and rMVA at weeks 16 and 24). The Dryvax group received the Dryvax vaccine (current smallpox vaccine) one and one half years prior to the DNA/MVA vaccine. The control group did not receive any vaccine. All macaques were challenged intrarectally with SIV251. Dryvax vaccination elicited a robust long-lived vaccinia-specific CD8 and CD4 responses. In the non-Dryvax group, Gag-specific CD8 and CD4 responses peaked following the second MVA boost with geometric mean frequencies of 0.14% and 0.47% of total CD8 and CD4 cells, respectively. These responses were 5-10 fold lower in the Dryvax group. Despite post vaccine cellular immunity being 5-10-times higher in the non-Dryvax animals, viral control was 100-fold better (p0.01) at peak viremia and 20-fold better at set point in the Dryvax than the non-Dryvax group. Retrospective analysis of vaccine elicited SIV-specific responses revealed enhanced expression of the lymph node homing receptor CCR7 on Gag-specific CD4 T cells in the Dryvax group compared to the non-Dryvax group (p0.01). A significant inverse correlation was observed between the frequency of Gag-specific CD4 T cells co-expressing CCR7 following vaccination and peak viremia following challenge (p=0.02). A significant inverse correlation was also observed between the frequency of Gag-specific CD8 T cells co-expressing IFN-g and IL-2 and peak viremia at 2 weeks following challenge (p0.01).Our results demonstrate that preexisting immunity to vaccinia lowers the magnitude of vaccine-elicited T cells but enhances control of SIV challenge by a DNA/MVA vaccine. This enhanced control correlated with better lymph node homing potential of the elicited T cells.
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