Abstract
Effective Tcell induction is an important strategy in HIV-vaccine development. However, it has been indicated that vaccine-induced HIV-specific CD4+ Tcells, the preferential targets of HIV infection, might increase viral acquisition after HIV exposure. We have recently developed an immunogen (CaV11), tandemly connected overlapping 11-mer peptides spanning the simian immunodeficiency virus (SIV) Gag capsid and Vif proteins, to selectively induce Gag- and Vif-specific CD8+ Tcells but not CD4+ Tcells. Here, we show protective efficacy of a CaV11-expressing vaccine against repeated intrarectal low-dose SIVmac239 challenge in rhesus macaques. Eight ofthe twelve vaccinated macaques were protected after eightchallenges. Kaplan-Meier analysis indicated significant protection in the vaccinees compared to the unvaccinated macaques. Vaccine-induced Gag-specific CD8+ Tcell responses were significantly higher in the protected than the unprotected vaccinees. These results suggest that classical CD8+ Tcell induction by viral Env-independent vaccination can confer protection from intrarectal SIV acquisition, highlighting the rationale for this immunogen design to induce virus-specific CD8+ Tcells but not CD4+ Tcells in HIV-vaccine development.
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