Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses.
Overall design: There are four protection outcome groups: unvaccinated control (C), complete protect (CP), non-protect (NP) and partial protect (PP). Respectively for these groups, there are 7, 9, 6 and 4 animals sampled seven days pre-challenge (minus7PCD); 9, 13, 5 and 5 animals sampled four days post-challenge (4PCD) and 8, 11, 5 and 3 fourteen days post-challenge (14PCD).
Less...