This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. To date we have completed the first cohort of 38 RM through both the vaccine and challenge phase, and have begun to perform immune correlates analysis comparing various immune parameters to outcome. A second cohort of 28 RM is schedule to begin in the next 2 months.
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