This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The development of an effective AIDS vaccine remains one of the highest priorities in HIV research. The live, attenuated varicella-zoster virus (VZV) Oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombinant vaccine against other pathogens, including human immunodeficiency virus (HIV). The simian varicella model, utilizing simian varicella virus (SVV), offers an approach to evaluate recombinant varicella vaccine candidates. Recombinant SVV (rSVV) vaccine viruses expressing simian immunodeficiency virus (SIV) env and gag antigens were constructed. The hypothesis tested was that a live, attenuated rSVV-SIV vaccine will induce immune responses against SIV in the rhesus macaques and provide protection against SIV challenge. The results demonstrated that rSVV-SIV vaccination induced low levels of neutralizing antibodies and cellular immune responses to SIV in immunized rhesus macaques and significantly reduced viral loads following intravenous challenge with pathogenic SIVmac251-CX-1. As a continuation of the previous study, this study evaluated additional immunological parameters to further define correlates of protection in these animals. Flow cytometry was conducted to show differences in stimulated memory lymphocyte subpopulations using CD3, CD4, CD8, CD28, CD95 and KI67 antibodies. Intracellular cellular cytokine assays tested functional characteristics of PBMCs following vaccination and challenge. Cryopreserved samples harvested 14 days following immunization, day of SIV challenge, and day 231 post SIV challenge were evaluated. Samples were stimulated with SIV peptides, stained with CD3, CD4, and CD8 surface markers and IL-2, TNF-A, and IFN-g. Results showed overall that experimental vaccinated animals have more polyfunctional CD4+ and CD8+ T cell SIVgag-specific responses compared with SIV env-specific responses. Increases in cellular proliferation and antigen specific polyfunctional cytokine responses in CD4 T helper cells may be crucial to control viral loads in vaccinated and SIV challenged macaques.
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