CORE--PRECLINICAL PRIMATE MODELS

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The objective of this core is to implement standardized protocols to test candidate vaccine antigens for immunogenicity and safety in non- human primates. Specific goals are to determine the optimal dose and route of administration required to obtain effective and persistent serum and reproductive tract titers of antibody of defined gamete antigens in the primate model. Particular attention will be paid to measuring and comparing the immune response to defined gamete antigens in oviductal fluids, cervical mucus and serum in Macaca fascicular is, the species chosen by the Contraception Development Branch for research focus. Specific functions of this core are: 1) to ensure the health and welfare of primates for immunologic and reproductive studies; 2) to inoculate monkeys with recombinant proteins and peptide immunogens; 3) to collect serum, oviductal fluid and cervical mucus from primate subjects; 4) to determine the quantity of antibody developed to specific immunogens in each animal over time; 5) to quantitiate the classes of antibodies arising to defined gamete antigens in each fluid using monkey-specific reagents; 6) to optimize immune responses by varying doses, formulations, routes and timing of antigen delivery; and 7) to determine the safety of specific immunogens. Information obtained from Core D is essential to prepare for large- scale contraceptive efficacy trials which are planned to be conducted mainly at the California Regional Primate Research Center (CRPRC) in Davis, once immunogenicity and safety evaluations have been completed in this core. However, it is anticipated that some efficacy tests may be performed in Core D at Virginia. This flexibility is required to minimize delays that may arise due to availability of monkeys and cages at each facility. Collaboration between the two Centers has been ongoing and exchange of information, monkeys, and monkey tissue has been beneficial. The data generated by the Core D and the CRPRC will help determine which antigens are suitable candidates for human clinical trials. In view of this, studies will focus on identifying the minimal dose which will optimize and and sustain immune responses.