Recombinant vector-induced HIV/SIV-specific CD4+ T lymphocyte responses in rhesus monkeys

The recently reported modest success of the RV144 Thai trial vaccine regimen in preventing HIV-1 acquisition has focused interest on the potential contribution to that protection of vaccine-elicited CD4⁺ T cell responses. We evaluated the induction of virus-specific CD4⁺ T cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitudes and functional profiles of the antigen-specific CD4⁺ T cells by measuring cytokine production, memory differentiation, and the expression of mucosal homing molecules. We found that DNA prime/recombinant MVA boost immunizations induced particularly high-frequency virus-specific CD4⁺ T cell responses with polyfunctional repertoires, and these responses were partially preserved following SHIV-89.6P challenge. The majority of the vaccine-elicited CD4⁺ T cells were CD28⁺ memory T cells that expressed low levels of β7. Neither the magnitudes nor the functional profiles of the virus-specific CD4⁺ T cells generated by vaccination were associated with a preservation of CD4⁺ T cells or control of viral replication following SHIV-89.6P challenge. Interestingly, monkeys primed with recombinant Ad5 immunogens showed a dramatic expansion of both the magnitude and polyfunctionality of the vaccine-elicited CD4⁺ T cell responses following envelope protein boost. These results demonstrate that vaccine strategies that include recombinant MVA or recombinant Ad5 vectors can elicit robust CD4⁺ T cell responses.