IMMUNOGENICITY STUDIES OF RABIES VIRUSES EXPRESSING HIV-1 OR SIV

点击翻译按钮获取中文摘要

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. Rabies virus (RV), a single-stranded RNA virus of the Rhabdovirus family, has recently been developed as a novel vaccine candidate for HIV-1. As a live-attenuated vaccine in mice, RV has been shown to induce vigorous and long lasting immune responses to both HIV-1 Env and Gag. Further, the single RV glycoprotein (G) can be functionally replaced by HIV-1 Env if the gp160 cytoplasmic tail domain (CD) is replaced by that of RV G. These surrogate, or G-deleted (DG), viruses expressing Env assume an HIV-1-like cell tropism and are therefore targeted to CD4+/HIV-1 co-receptor positive cells. This report describes a proof of principle study of the safety, replication capacity and immunogenicity of G-deleted RV expressing Env in rhesus macaques. The results show these viruses can productively infect rhesus peripheral blood mononuclear cells (PBMCs) and vaccinated animals seroconvert to the RV ribonucleic acid particle (RNP). An animal vaccinated with a G-deleted virus expressing the SHIV-89.6P envelope developed high titer virus neutralizing antibodies and Env-specific cellular immune responses post-challenge with SHIV-89.6P. Importantly, there was no evidence of CD4+ T-cell loss and plasma viral loads were controlled to undetectable levels by six weeks post-challenge. The animal has remained healthy with no signs of disease up to twenty-two weeks post-challenge.