The aim of this project is to test in rhesus macaques the efficacy of various live vectors carrying human immunodeficiency virus type-1 (HIV-1), HIV-2 and simian immunodeficiency virus (SIV) antigens in eliciting a protective immunoresponse. We are testing three different delivery systems: 1) attenuated vaccinia and avipox carrying HIV and SIV antigens; 2) attenuated Salmonella typhimurium strain and the Bacille of Calmette and Guerin (BCG), as a bacterial vaccine, carrying HIV/SIV antigens. We are also planning to further stimulate the immunoresponse in the immunized animals using purified viral antigens (either native or recombinant viral subunits). We will use rhesus macaques which are susceptible to the infection of both SIV(mac251) and HIV-2(SBL/ISY). The end point of our studies will be the protection from infection by either SIV or HIV-2. Vectors containing HIV-1 antigens will also be evaluated for their immunogenicity in rhesus macaques. The infectivity of HIV-2 mutants performed in vitro and in vivo provided a better choice for the HIV-2 virus to be used in homologous challenge experiments.