Background:  An important goal in the development of a vaccine for HIV-1 is the induction of cell-mediated immune responses able to contain viral replication.

Methods:  A study was designed whereby vaccination of macaques with DNA expressing the Gag and Env proteins of SIV followed by immunizations with the highly attenuated recombinant poxvirus-based NYVAC-SIV-gag-pol-env vaccine candidate (NYVAC-SIV-gpe) was compared with immunization with NYVAC-SIV-gpe alone. 

Results: Upon mucosal challenge exposure to SIVmac251, the DNA-gag-env/NYVAC-SIV-gpe vaccinated macaques mounted a secondary immunological response of sufficient quantity to contain replication of the highly pathogenic SIVmac251 virus.   A significant reduction of viremia level was observed during both the acute and chronic phases of infection in these macaques.  The degree of viremia containment correlated with the prechallenge level of lymphoproliferative responses to the core and envelope proteins of SIV and to the CTL response to the immunodominant epitope Gag181 (p11C-M) in Mamu-A*01-positive macaques.  In these animals, the CTL response during the acute phase of infection was mainly focused on the 2 immunodominant epitopes, Gag181 (p11C-M) and Tat28.  

Conclusions:  Although the DNA prime NYVAC-SIV boost vaccine regimen did not provide sterilizing immunity, it was associated with a significant reduction of viral replication.