This is a multidisciplinary molecular virology and immunology program project grant to develop and test DNA and protein immunogens for immunodeficiency virus vaccines. Vaccine trials will be run at the Yerkes Regional Primate Research Center using rhesus macaques and graded SHIV-89.6 challenges. In project 1, Dr. Harriet Robinson will develop DNA immunogens and evaluate humoral responses. Vaccine DNAs will be designed to express non-infectious SHIV-89.6 particles (VLP) and test new concepts for improved humoral responses. In project 2, Dr. Richard Compans of Emory School of Medicine will develop SHIV-89.6 VLPs as well as 89.6 fusion proteins for testing new concepts for raising long-lasting neutralizing antibody. In project 3, Dr. John Altman will work with Dr. Kelly MacDonald of the University of Toronto and Dr. Brian Barber of Connaught Labs Canada to type and assign macaques to MHC-matched trial groups, to identify MHC motifs, and to construct MHC tetramers for follo wing T-cell receptor responses. In project 4, Dr. Francois Villinger of the Emory School of Medicine and Dr. Janet McNicholl of the Centers for Disease Control and Prevention will use novel, as well as more conventional, assays for scoring the CD4 and CD8 T-cell responses raised by the different vaccine protocols. Drs. Harold McClure and Shawn O'Neil of the Yerkes Regional Primate Research Center will provide a primate core and assays for quantitative virus load. Dr. Harriet Robinson provides administrative support to the projects. The first vaccine trial in macaques will use a SHIV-89.6 VLP DNA prime and protein boost in groups comparing (i) intramuscular and gene gun inoculations for immunogenicity and protective efficacy, (ii) the potential of co-inoculated genetic adjuvants (GM-CSF plus IL-12 or IL-18) to improve immunogenicity and protection, and (iii) the ability of an ubiquitinated SHIV-89.6 library to improve protection. The second vaccine trial will build on parameters id entified as promising in the first trial, and test new concepts developed in Projects 1 and 2. FUNDING NIH / NIAID $750,000 8/01/98 - 3/31/03 PUBLICATIONS Robinson, H.L., Candido, M.A., Lydy, S.R., Herndon, J.G., McClure, H.M., et.al. Neutralizing Antibody-Independent Containment of Immunodeficiency Virus Challenges by DNA Priming and Recombinant Pox Virus Booster Immunizations, Nature Medicine (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center