This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study evaluated the protective potential of the HIV-1 regulatory protein, Tat, as a purified biologically active protein and as a gene product expressed by a recombinant replication-competent adenovirus vector in Macaca fascicularis of Mauritius origin. One group of macaques (Group 1) received nine separate vaccinations with Tat protein, divided between subcutaneous (with alum adjuvant) and intradermal (no adjuvant) routes. Group 2 received two vaccinations, one intranasal and one intratracheal. This group of animals was boosted with Tat protein at weeks 24 and 36. Two groups of three macaques that received alum only or empty vector serve as control groups. Immune responses for the two intervention groups are being assayed by ELISA, Luminex multianalyte profiling (xMAP), T-cell IFN-' ELISPOT, intracellular cytokine staining, proliferation assays and HIV neutralization in vitro. Mucosal secretions are being assayed by ELISA. Additionally, cellular immunity at a mucosal site is being monitored by taking rectal pinch biopsies prior to the first vaccination and at weeks 13 or 14 and 38. The new xMAP system is being evaluated in comparison to the standard Tat ELISA. The results show that Group 1 animals mounted a rapid and sustained binding antibody response. Group 2 animals had lower antibody levels following the adeno-recombinant immunizations that rose quickly following the protein boosts. Cellular immune response assays showed that T-cell responses were induced in both the adeno-recombinant group and the protein group with the former exhibiting higher activity than the latter.
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