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Abstract: Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4+ T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4+ T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8+ tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer+ T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4+ T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer+ T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4+ T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4+ T cell levels and SIV viral load. [ABSTRACT FROM AUTHOR]

Abstract: HIV-1 specific cellular immune responses play a significant part in controlling HIV-1 viral replication and are an important component of an HIV-1 vaccine induced immune response. We reported earlier that recombinant DNA vaccine delivered intramuscularly, and recombinant Listeria monocytogenes, delivered orally induced CD8+ and CD4+ T cell immune responses in rhesus macaques and that this vaccine protocol showed partial protection against an SIV239 challenge. In this paper, we have analyzed the SIV antigen-specific immune responses at the time of challenge and during the subsequent infection course. We find that the immune status of the animals, as measured by the frequency of antigen-specific IFN-gamma secreting peripheral blood mononuclear cells, at the time of challenge correlates more strongly with viral loads at set point than peak viral loads. The correlation between the immune response and viral load was strongest early, as viral set-point was just being established and disintegrates overtime. This study demonstrates the cellular immune response to SIV at the time of challenge of a nonhuman primate is able to impact on viral set-point following SIV239 challenge. Further, this study demonstrates that as virus replicates the T cell immune response to SIV antigens induced by the vaccine is modulated by antigen encountered by immune cells during viral replication. [Copyright &y& Elsevier]