Simian immunodeficiency virus-specific cytotoxic T lymphocytes and protection against challenge in rhesus macaques immunized with a live attenuated simian immunodeficiency virus vaccine

In this study, we examined the role of simian immunodeficiency virus (SIV)- specific cytotoxic T lymphocytes (CTLs) in macaques immunized with an atten uated strain of simian immunodeficiency virus (SIVmac239 Delta nef) in prot ection against pathogenic challenge with SIVmac251. Our results indicate th at attenuated SIVmac239 Delta nef can elicit specific CTL precursor cells ( CTLp), but no correlation was observed between breadth or strength of CTLp response to structural proteins SIV-Env, -Gamg or -Pol (as measured by limi ting dilution assay) and protection against infection. In one animal, we lo ngitudinally followed the SIV-Gag-specific response to an MHC class I Mamu- A*01-restricted epitope p11C, C-M using a tetrameric MHC/peptide complex re agent. A low frequency of SIV p11C, C-M peptide-specific tetramer-reactive cells was present at the lime of challenge but could be expanded in vitro. Surprisingly, the tow level of Mamu-A*01/p11C, C-M-specific CTLs induced th rough attenuated SIVmac239 Delta nef vaccination increased in the absence o f detectable SIVmac251 or SIVmac239 Delta nef proviral DNA. Overall, our re sults suggest that protection against infection in this model can be achiev ed through more than one mechanism, with SIV-specific CTLs being important in controlling SIVmac239 Delta nef viral replication postchallenge. (C) 200 0 Academic Press.