HIV infection in China has been increasing rapidly since 1995 and the infected people may reach 10 million by year 2010. An effective vaccine is our best hope to prevent and control the spread of HIV infection and AIDS. The major goal of this project is trying to get the novel recombinant HIV/AIDS vaccine which could efficiently eliminate the HIV infection and possibly supply a cross protection against the infection with different HIV subtypes. We hypothesize that a successful HIV/AIDS vaccine may mainly depend on its ability on induction of efficiently protective CTLs to abort the virus replication at the early stage before the viruses are completely assembled, and the neutralization antibodies are needed to help the CTLS effectively to play their roles through decreasing the virus load. To develop a novel HIV/AIDS vaccine, this application proposes to use a unique non-replicated vaccinia vector NTV derived from vaccinia virus Tiantan vector NTV derived from vaccinia virus strain, a genetically detoxified anthrax lethal toxin (Gdalt) and a replicable DNA vaccine vector (rDNA) in optimal combination to stimulate both efficient cellular and humoral immune responses against HIV/AIDS. We have made the following specific aims to reach the goal: 1. Constructing three classes of HIV-1 vaccine candidates based on NTV, Gdalt, and rDNA vector using HIV-1 antigens of Chinese origin. Selecting the early genes such as pol, nef, tat, rev and middle late gene gag to induce efficient CTLs and the env gene, gp160, to elicit neutralizing antibody; 2. Optimizing the combined immunization protocols of the vaccine candidates in animals; 3. Developing the vaccine candidates through process of pilot productions and pre-clinical toxicology tests, thus obtaining SDS approval; 4. Preparation for Phase I and II human trials. In this project, all the selected genes will match with the epidemic strain investigated in this CIPRA program. And the human trials will be carried out in the area of cohort studies (the research project 1-3 in this CIPRA program and the undergoing HPTN or NIH). The achievements of the specific aims in this project will not only contribute to the development of HIV/AIDS vaccine in China but also be benefit to the prevention and control of HIV/AIDS in other countries.