beneath the table to the abstract. Use the Word Count cmd under Utilites menu for counting Significance These studies should provide insight into the use of recombinant Listeria monocytogenes for generating anti-viral mucosal immunity in primates. Because live-attenuated bacterial vaccines are currently used in people, this work may lead directly to a vaccine that can be used to prevent the sexual transmission of HIV. Objectives This project will use the SIV/macaque model to test the efficacy of immunization with recombinant Listeria monocytogenes, an attenuated, intracellular bacterium. Initial studies will characterize the pathogenicity in rhesus monkeys of attenuated Listeria vectors, and immune responses of rhesus macaques to the proteins of SIV expressed by these vectors. Anti-SIV cytotoxic T lymphocyte responses in peripheral blood, lymphoid tissues and the genital mucosa will be quantified. And systemic and secretory (including vaginal) immune responses to the immunizations will be characterized using isotype and SIV-specific assays. If a strong local immune response is produced by the immunization strategy, the animals will be vaginally challenged with virulent SIV. Results Initial immunization of 4 juvenile monkeys with Listeria expressing the SIV gag gene and of 2 monkeys with a control Listeria was found to be nontoxic, with doses ranging from 105 to 108 colony forming units given intramuscularly. All 6 monkeys became infected with SIV after oral challenge, with viral loads similar to unimmunized monkeys. Future Directions Monkeys will be immunized by the oral or intranasal route with the Listeria vector, instead of the intramuscular route. Viability of the Listeria vaccine strain will be tested in rhesus monkey macrophage in the laboratory. KEY WORDS SIV, vaccine, cell-mediated immunity, Listeria FUNDING NIH Grant AI39427
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