Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) are currently the most effective vaccines in nonhuman primate models for AIDS, yet the basis of their robust protection remains poorly understood. Our recent immune correlate study revealed that degree of protection against pathogenic SIV challenge strongly correlated with the SIV-specific CD4+ and CD8+ T cell responses in the lymph node but neither with the responses of such T cells in the peripheral blood and mucosal tissues nor with humoral immune responses. Interestingly, the maintenance of protective T cell responses in the lymph node was associated with the amount of persistent LAV replication in the lymph node, which localized almost exclusively in follicular helper T cells. The protected monkeys manifested greater magnitude of functional effector CD8+ T cells in the lymph node, suggesting that the induction and maintenance of antiviral effector memory T cells derived by persistent antigen production have a vital role in establishment of protection. This article reviews the mechanisms of the protection in monkeys vaccinated with LAV and their implication for development of successful AIDS vaccine.
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