Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV 89.6P challenge in Mamu-A⁎01 negative rhesus macaques

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 SIV mac251 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 89.6P model. All groups were primed with Ad-HIV env 89.6P , SIV gag 239 , and SIV nef 239 recombinants. One group was not boosted, one received HIV 89.6Pgp140ΔCFI protein, and one a novel HIV-1 poly-peptide “peptomer”. The HIV 89.6Pgp140ΔCFI 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.