For RhCMV/SIV-induced MHC-E restricted CD8+ T cell-mediated protection in RMs, some SIV replication and spread occur early after effective challenge, as evidenced by direct viral measurements in tissues in the first few weeks following infection and by the post-challenge induction of T cell responses to SIV antigens (Ags) not included in the vaccine (e.g., anti-Vif and anti-Env T cell responses) (Hansen et al., 2013a; Picker et al., 2023). Here, CD8A is linked to infection.