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. Sequential vaccination with three different live recombinant vesicular stomatitis (VSV) vectors expressing SHIV proteins provides long-term protection from AIDS in the rhesus macaque/SHIV89.6P challenge model. Protection from AIDS and even faster control of challenge virus load was also achieved using a VSV prime, MVA vector boost strategy. Because the SHIV 89.6P challenge model has been criticized as being 'too easy' to protect against, we have tested the VSV prime, MVA boost strategy in the more stringent SIVmac251 challenge model. Eight Chinese-origin rhesus macaques were vaccinated with a mixture of four VSV vectors (G Indiana serotype envelope) optimized for production of SIVmac239 Gag, Pol, Env, and a polyprotein of Rev-Tat-Nef-Vif sequences (Retanif). These animals were boosted with three MVA vectors expressing SIVmac239 Gag-Pol, Env, and the Retanif polyprotein. A second boost was performed with VSV vectors (G Chandipura envelope) expressing the same SIVmac proteins. Seven control animals received VSV vectors expressing an irrelevant influenza antigen, and empty MVA vectors on the same schedule. Rectal challenge with SIVmac251was performed at about two months after the final boost in all sixteen animals. One animal in each group was not infected after challenge. Comparing the animals in each group that became infected, the vaccinated group had significantly better (10 fold) control of average virus loads at peak viremia (day 14) post-challenge. However, there was no significant difference in plasma viral loads between vaccinees and controls during the chronic phase of SIVmac251 infection. No significant cellular immune responses (by Elispot) as well as SIV neutralizing antibodies were detected in either group. Thus far, 4 of the 8 vaccinees and 3 of the 7 controls developed AIDS.
Showing the most recent 10 out of 352 publications
