Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques |
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Authors: | Patterson L Jean Beal Jennifer Demberg Thorsten Florese Ruth H Malkevich Nina Venzon David Aldrich Kris Richardson Ersell Kalyanaraman V S Kalisz Irene Lee Eun Mi Montefiori David C Robey Frank A Robert-Guroff Marjorie |
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Affiliation: | Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA. |
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Abstract: | Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv89.6P, SIVgag239, and SIVnef239 recombinants. One group was not boosted, one received HIV89.6Pgp140DeltaCFI protein, and one a novel HIV-1 poly-peptide "peptomer". The HIV89.6Pgp140DeltaCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected. |
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Keywords: | Replicating adenovirus vectors prime/boost HIV/SIV vaccines SHIV89.6P challenge Rhesus macaques |
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