Recombinant Listseria Monocytogenes as an SIV Vaccine

NON-TECHNICAL SUMMARY: The use of recombinant Listeria monocytogenes for generating anti-viral mucosal immunity in primates are a promising vaccine candidate in the treatment of AIDS 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.

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APPROACH: The 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 ELISA and Western blot assays. We will also determine the immune response between each boost in order to assess which components of the immunization protocol are essential to obtain a maximum response. Thus, oral immunization may be sufficient to generate an effective genital immune response or it may be necessary to boost the animals with vaginal and systemic immunizations. If a strong local immune response is produced by the immunization strategy, the animals will be vaginally challenged with virulent SIV.
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PROGRESS: 1999/12 TO 2004/11<BR>
Most HIV infections occur by transmission across mucosal surfaces where dendritic cells (DCs) are the first cells to encounter the virus. This project used a novel in vitro assay of SIV replication in DCs co-cultured with autologous CD4+ T cells and monocytes, suppression of viral replication was detected from 5 of the 6 monkeys at multiple timepoints before and after SIV challenge. The Primate Center at UC Davis is now no longer administered by the School of Veterinary Medicine, therefore we will no longer be monitoring this project and it will be terminated in the CRIS system.
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IMPACT: 1999/12 TO 2004/11<BR>
Optimizing this immunization strategy may results in a strong antiviral DTH response that could control a primary lentiviral infection.