The ultimate application of the proposed research is the development of vaccines for HIV. The express goal of the research is to use a novel approach to first develop a vaccine that will provide immunity against SIV in a simian AIDS model. A basic premise of the Research Plan is the desirability of initiating immunity at mucosae that are natural sites of infection with HIV.
SPECIFIC AIM 1. Chlamydia trachomatis (Ct) will be used as a vaccine """"""""vector"""""""" for SIV genes because it naturally infects mucosae. The gag, nef, tat and rev SIV genes will be introduced into Ct by the use of homologous recombination vectors (HRV): plasmids in which SIV genes are flanked by segments of Ct chromosomal DNA. Ct transformants (Ct(SIV)) resulting from such recombinations, will be isolated by selection for a selection gene that is also present in the HRV.
SPECIFIC AIM 2. The expression of SIV genes in Ct(SIV) strains will be studied both in vitro and in vivo. Expression will be examined in HeLa cells and immunogenicity studies will be carded out in Cynomolgus macaques.
SPECIFIC AIM 3. The ability of Ct(SIV) strains to induce immunity that might reduce rate of infection or ameliorate disease course after SIV challenge will be investigated by repeatedly challenging (intravaginally, i.vag.) cynomolgous macaques with a low dose of SIVmac239. Immune responses to the SIV proteins encoded in the Ct(SIV) strains will be monitored, as will the outcome after challenge with SIV. This is a first attempt to use Chlamydia as a vaccine vector to induce immune responses at mucosae. Subsequent experiments might include the use of attenuated strains of Chlamydia vectors to deliver additional SIV genes (Env and Pol). However, the immediate goal of this limited R21 application is to explore the innovative idea of using Chlamydia as a vaccine vector.
