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. This study is designed to characterize host innate and/or adaptive immune responses that have the capacity to protect against pathogenic SIV infection in rhesus macaques, and by extension, HIV-1 infection of humans. To accomplish this goal we will start with the best characterized model of vaccine-induced protection - the live attenuated vaccine model (LAV) in rhesus macaques - and determine the immune parameters that correlate with this protection. The plan of this project is therefore to immunize rhesus macaques with a live attenuated SIV vaccine known to provide complete SIV protection as well as with other LAV and non-LAV approaches that provide partial protection. We will then generate a comprehensive data matrix profile comparing the immunologic, virologic and genetic parameters of vaccinated animals and correlate these parameters with protection from highly pathogenic homologous SIV challenge. This will be the most comprehensive immune analysis in the rhesus macaque - SIV model, including comprehensive assessment of both innate (using gene array technology) and adaptive immunity (cellular and humoral), and determination of the genetic and virologic components of protection. Factors that best correlate with protection will be validated in further collaborative studies in macaques using a more stringent heterologous pathogenic SIV challenge. In the last year we have completed analysis of cohort #1, a group of 32 RM administered different LAVs so as to create an immune correlates matrix: that is, a broad spectrum of immune response measurements and different outcomes after pathogenic SIV challenge, so as to allow statistical analysis of immune correlates. In this cohort, we found a strong statistical signal with regard to prediction of outcome with the magnitude of SIV-specific T cell responses in peripheral lymph node but not other sites. Current work is directed at understanding the mechanisms of this correlation. A manuscript describing these findings is currently being prepared.
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