Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV sub(8) sub(9) sub(.) sub(6) sub(P) challenge in Mamu-A approximately equal to 01 negative rhesus macaques

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 SIV sub(m) sub(a) sub(c) sub(2) sub(5) sub(1) challenge. Both Env-specific antibody mediatin...

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Veröffentlicht in:Virology (New York, N.Y.) N.Y.), 2008-05, Vol.374 (2), p.322-337
Hauptverfasser: Patterson, L J, Beal, J, Demberg, T, Florese, R H, Malkevich, N, Venzon, D, Aldrich, K, Richardson, E, Kalyanaraman, V S, Kalisz, I, Lee, E M, Montefiori, D C, Robey, F A, Robert-Guroff, M
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Sprache:eng
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Zusammenfassung: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 SIV sub(m) sub(a) sub(c) sub(2) sub(5) sub(1) 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 SHIV sub(8) sub(9) sub(.) sub(6) sub(P) model. All groups were primed with Ad-HIVenv sub(8) sub(9) sub(.) sub(6) sub(P), SIVgag sub(2) sub(3) sub(9), and SIVnef sub(2) sub(3) sub(9) recombinants. One group was not boosted, one received HIV sub(8) sub(9) sub(.) sub(6) sub(P)gp140 Delta CFI protein, and one a novel HIV-1 poly-peptide ''peptomer''. The HIV sub(8) sub(9) sub(.) sub(6) sub(P)gp140 Delta CFI 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.
ISSN:0042-6822
DOI:10.1016/j.virol.2007.12.037