HARNESSING INNATE IMMUNITY TO ENHANCE T-CELL INDUCING HIV VACCINES

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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 project is part of a large consortium on AIDS vaccine development sponsored by the Gates Foundation. The overall project is designed to determine the effects that triggering various elements of the innate immune system during vaccination has on the subsequent adaptive immune response against the vaccine, particularly the T cell response. Dr. Picker is supervising the nonhuman primate component of this project, which has the following goals: 1) development of protocols to apply selected vaccines [protein + adjuvant(s) or microbial vectors] incorporating SIV or HIV gene products to monkey cohorts, 2) selection of appropriate study animals, 3) implementation of these protocols with these monkeys, 4) provision of clinical care/monitoring for study monkeys, 5) collection of samples from monkey subjects, 6) distribution of these samples to the appropriate testing laboratories for analysis, 7) determination of the kinetics of the adjuvant-induced immune response locally, in draining lymph nodes, and distal sites systemically and mucosally, 8) assessment of the quality and quantity of T cell responses generated by the vaccination protocols, and 9) determination of the efficacy of the vaccination protocols to be studied. Work under the auspices of this project has identified the TLR3 and RIG-I agonist poly I:C as a superior adjuvant for eliciting both Ab and T cell responses to SIV proteins. Currently, we are performing a large efficacy trial of poly I:C adjuvanted SIVenv protein to provide anti-SIVenv antibody responses that would prevent acquisition of highly pathogenic SIV after repeated limiting dose intra-rectal challenge.