MODULATION OF EARLY HOST RESPONSE TO SIV IN PATHOGENIC INFECTION

Emory University, Atlanta GA

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Abstract

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 project is aimed to delineate differences in the initial immune responses to immunization with HSV encoded SIV proteins to compare sooty mangabeys (disease resistant model) with rhesus macaques (SIV disease susceptible model) and identify mechanistic differences potentially affecting (immunopathologic) responses to SIV infection. The grant proposal will use a replication deficient recombinant Herpes simplex based vector expressing SIV gag, env and tat-rev-nef of SIVmac239 to immunize sooty mangabeys via intra-muscular (n=3), intra-nasal (n=3) or intra-rectal (n=3) delivery. All animals will be followed for about 6 months thereafter for responses in blood, lymph nodes, lung and GI mucosa. The animals will then be released back to the Center. The animals will be screened first for SIV, STLV and SRV and only those found negative will be included. In addition, 6 sooty mangabeys chronically infected with SIV will be sampled once in years 4 and 5 for responses in blood, lymph nodes, lung and GI mucosa. The data obtained form the Yerkes sooty mangabeys will be compared to data obtained using the identical protocol performed at the New England National Primate Research Center using rhesus macaques.