A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT

University Of Wisconsin-Madison, Madison WI

Investigators

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Abstract

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. To generate strong cytotoxic T lymphocytes (CTL) responses, in the absence of other immune responses, using [unreadable] several different vaccine approaches.[unreadable] [unreadable] In this study, we vaccinated 8 Mamu A*01 rhesus macaques with DNA and Adenovirus vectors encoding Gag, Tat, Rev and [unreadable] Nef proteins from SIVmac239. The vaccinees, along with 8 control animals, were challenged multiple times with a low [unreadable] dose of SIVmac239 by the intrarectal route. After challenge, the vaccinees as a group were able to control viremia to [unreadable] nearly two logs lower than the control group at one year post-challenge. By two years post challenge, most of the control [unreadable] group has been euthanized. The remaining vaccinees have separated into animals that continue to control viremia well [unreadable] and those that have not. Those that control viremia have higher CD4+ T cells in both the PBMC and BAL. They have [unreadable] increased numbers of tetramer positive CD8+ T cells in the mucosa, even higher than in the PBMC. While we cannot tell if [unreadable] these results are cause or effect, the result is that you have CD4+ T cells and CTL that are specific for SIV epitopes in the [unreadable] mucosal areas, where they are most needed. In 2007, we are starting a new study in which we vaccinate with all SIV [unreadable] proteins except Env. This research uses WNPRC Immunology and Virology Services.[unreadable]