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. Vaccines based on replication-defective adenoviral vectors are being developed for infectious agents and tumor-associated antigens. Early work focused on vaccines derived from a common human serotype of adenovirus, AdHu5. Neutralizing antibodies against AdHu5 virus, present in a large percentage of the human population, damp the efficacy of vaccines based on this carrier. To circumvent this problem, we developed vectors derived from chimpanzee adenoviruses. Immunization of monkeys with rAd5-Clade B Env + SIV Gag-pol elicited higher cellular immune responses than immunization with either of the chimpanzee adenoviruses as assessed by PBMC IFN-gamma ELISpot assays using pooled peptides. Following challenge with SHIV-89.6P, control monkeys showed a dramatic decline in their CD4 T cell numbers. These monkeys had a peak viral load of 8 log copies/ml of plasma. Monkeys immunized with either Chimpanzee adenovirus Pan7 or rAd5 had preserved CD4 T cells. These groups of monkeys also had lower peak and set-point viral RNA levels than the control animals. 5 of the 6 Monkeys immunized with Pan9 adenovirus had a greater loss of CD4 T cells compared to the Pan7 and rAd5 groups. These data suggest that some chimpanzee adenovirus vectors elicit immune responses lower in magnitudes than that induced by human adenovirus type 5 vectors. But these vaccine vectors provide comparable protection against pathogenic viral challenge in a nonhuman primate model.
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