This cooperative vaccine development program will combine the resources and expertise of 4 institutions to develop and evaluate prototype AIDS vaccines using the HIV-related simian immunodeficiency virus (SIV). Vaccines will be evaluated both for the ability to prevent SIV infection of rhesus monkeys and to inhibit disease progression. since the characteristics of the disease produced by the challenge inoculum have been well-defined. Five interrelated projects involving different vaccine approaches will utilize the same core facilities at the Delta Regional Primate Research Center for identification of essential vaccine components, definition of protective responses, and comparative assessment of vaccine efficacy. Project 1, performed at the Delta Regional Primate Research Center, will prepare whole virus vaccines by various methods of inactivation, evaluate the retention of important immunoreactive epitopes, and evaluate protection augmented with the most potent adjuvants available. The role of humoral immune responses in protection will also be addressed in passive immunization studies. Project 2, performed at the Louisiana State University (LSU) School of Veterinary Medicine, will identify T-cell epitopes on SIV proteins and develop epitope- specific cellular immune assays to be used in defining protective immune responses and in vitro evaluation of vaccine-induced immunity. Project 3, conducted at the LSU Department of Biochemistry will use synthetic peptide technology and protein purification procedures to identify SIV immunoreactive epitopes and assess antigenic variation of SIV isolates. Project 4, conducted at Repligen, Inc., will utilize monoclonal antibodies, viral proteins and protein fragments produced by recombinant DNA technology to identify neutralizing epitopes and construct recombinants proteins for use in vaccine evaluations. Project 5, conducted at DRPRC, will utilize anti-idiotype pre-immunization to alter idiotype network regulation of the immune response to SIV in order to activate normally silent clones of immune cells. The combined projects will produce and share a broad range of synthetic and recombinant viral components, immune sera and monoclonal antibodies that will enable detailed evaluation of immune responses to vaccines and identification of components essential for protection.
