Background:  Virus-specific cytotoxic T lymphocytes (CTL) play an important role in the control of immunodeficiency virus infections. Recently, several CTL-based AIDS vaccine trials in macaques showed control of replication of SHIV89.6P that induces acute AIDS. However, it is becoming increasingly clear that SHIV89.6P may not be an appropriate challenge virus, and none of these vaccine regimens have been successful in the containment of the more realistic challenge of SIV that induce chronic AIDS. Thus, previous studies have failed to show CTL-based control of SIV replication.

Methods: Eight rhesus macaques vaccinated with DNA-prime/Gag-expressing Sendai virus (SeV-Gag) vector-boost were challenged intravenously with SIV_mac239. Antigen-specific T-cell levels were measured by flow-cytometric detection of antigen-specific interferon-<,greek>gamma</GREEK> induction. SIV gag fragment was amplified by RT-PCR from plasma RNA at week 5 after challenge, subcloned into plasmids, and sequenced.

Results:  Gag-specific CD4⁺ and CD8⁺ T cells were induced efficiently in all of the vaccinees after SeV-Gag booster; 5 of the vaccinees controlled SIV_mac239 replication after challenge and had undetectable plasma viremia after 5 weeks of infection. All 5 of the macaques that controlled SIV replication, but not those that did not, showed extremely rapid selection of CTL-escape mutant, suggesting that vaccine-induced CTL successfully contained replication of the challenge virus.

Conclusions:  Our study, for the first time, shows control of SIV_mac239 replication by vaccine-induced Gag-specific CTL, suggesting that vaccine induction of highly effective CTL can result in the containment of a highly pathogenic immunodeficiency virus. This work indicates the rationale for development of a CTL-based AIDS vaccine and has an important implication for vaccine design.

Keywords: CTL; SIV; AIDS vaccine