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. A critical roadblock in the development of an HIV-1 vaccine is our current inability to deliver HIV-1 antigens efficiently to the immune system and to prime predictable, high frequency immune responses in humans. For example, plasmid DNA and recombinant poxvirus vaccines are inefficient at expressing antigens and have proven poorly immunogenic in humans to date. In contrast, recombinant adenovirus serotype 5 (rAd5) vector-based vaccines have demonstrated impressive immunogenicity in animal models and are therefore being advanced into large-scale clinical trials. However, the high frequency of pre-existing immunity to the Ad5 vector in the developing world will likely substantially blunt the immunogenicity and clinical utility of rAd5 vaccines for HIV-1. To overcome this hurdle, we are developing novel replication-incompetent rAd vector-based vaccines derived from rare Ad serotypes. We immunized rhesus monkeys with rAd5, rAd35, chimeric rAd35k5, and chimeric rAd5HVR48 vectors expressing SIV Gag and HIV-1 Env to explore the immunogenicity of these candidate vaccines.
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