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149 Novel Vectors and Antigens for a Next Generation HIV-1 Vaccine

Barouch, Dan H

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 61
doi: 10.1097/01.qai.0000397334.95234.47

Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA

Alternative serotype Ad vectors such as rAd26 and rAd35 are biologically substantially different than rAd5 vectors. We have evaluated rAd26 and rAd35 vectors expressing SIV antigens in immunogenicity and challenge studies in rhesus monkeys, and we have recently advanced a prototype rAd26 vector expressing HIV-1 Env into a phase 1 clinical trial. Importantly, this vector has proven safe and immunogenic in humans at doses of 109 vp, 1010 vp, and 1011 vp. We have also assessed the capacity of vector-specific CD4+ T lymphocytes to traffic to mucosal surfaces following rAd vaccination in rhesus monkeys, and we have observed that trafficking of vector-specific CD4+ T lymphocytes to colorectal mucosa does not occur more readily in monkeys with baseline vector immunity as compared with monkeys without baseline vector immunity. In addition, we have demonstrated that computationally optimized “mosaic” HIV-1 Gag/Pol/Env antigens substantially expand cellular immune breadth and depth as compared with consensus or natural sequence antigens in rhesus monkeys. Taken together, these data suggest that a rAd35/rAd26 prime-boost vector regimen expressing mosaic HIV-1 antigens should be evaluated in clinical studies.

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