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. Although live, attenuated vaccines can provide potent protection against heterologous SIV and SHIV challenge, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8+ lymphocytes contribute to this vaccine-induced protection, we depleted vaccinated rhesus macaques of CD8+ lymphocytes, then challenged them SIVmac251 by the IV route. While vaccination with SIVmac239delta3 did not block infection with challenge virus, the post-challenge levels of plasma virus in control antibody-treated animals were significantly lower than in unvaccinated animals. Depletion of CD8+ lymphocytes at the time of challenge resulted in intermediate median plasma virus levels that were between the vaccinated and unvaccinated controls suggesting the cell-mediated immune responses contributed to, but were not solely responsible for, protection. Interestingly, at the time of challenge, animals expressing Mamu A*01 showed significantly higher frequencies of SIV-specific CD8+ T cell responses and lower neutralizing antibody titers than Mamu A*01- animals. Consistent with this finding, depletion of CD8+ lymphocytes abrogated vaccine-induced protection to a greater extent in Mamu A*01+ than in Mamu A*01- animals. These results indicate that live-attenuated SIV vaccines can provide protection by inducing both humoral and cellular immune responses and the relative contribution of each of these responses to protection is genetically determined.
Showing the most recent 10 out of 365 publications