Extralymphoid CD8 ⁺ T cells resident in tissue from simian immunodeficiency virus SIVmac239△nef-vaccinated macaques suppress SIVmac239 replication ex vivo

Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239△nef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239△nef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-γ) enzyme-linked immunospot assay at select time points; however, we found that lung CD8 ⁺ T cells, unlike blood CD8 ⁺ T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239△nef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV.