Acquired Immunodeficiency syndrome (AIDS) is a severe immunodeficiency disease which follows infection with the human retrovirus human immunodeficiency virus (HIV). The severity of the disease and the evolution of a pandemic makes the development of an effective HIV vaccine one of the highest priorities in current biomedical research. In collaboration with Applied Biotechnology, Inc. we will test the in vitro efficacy of recombinant vaccinia viruses expressing HIV proteins as potential vaccine candidates in humans by : 1. Assessing HIV specific, MHC restricted CTL responses and ADCC activity in HIV infected humans using target cells infected with recombinant vaccinia viruses expressing HIV antigens. 2. Assessing HIV strain specificity of CTL responses and ADCC activity in HIV infected humans using target cells infected with recombinant vaccinia viruses expressing HIV antigens. 3. Assessing determinants within GAG and ENV proteins responsible for CTL responses and ADCC activity in HIV infected humans using target cells infected with recombinant vaccinia viruses expressing HIV antigens. 4. Determining the level of neutralizing antibody production in mice and primates after vaccination with prototype recombinant vaccinia virus vaccines. 5. Assessing HIV strain specificity of neutralizing antibody activity induced in mice and primates after vaccination with prototype recombinant vaccinia vaccines. The development of an HIV vaccine which is a potent inducer of both humoral and cell-mediated immunity offers hope for the prevention of future infections with this devastating virus.