A novel immunogen selectively eliciting CD8+ T cells but not CD4+ T cells targeting immunodeficiency virus antigens

Optimization of immunogen is crucial for induction of effective T-cell responses in the development of an HIV vaccine. Conventional T cell-based vaccines have been designed to induce virus-specific CD4(+) T as well as CD8(+) T cells. However, it has been indicated that induction of HIV-specific CD4(+) T cells, preferential targets for HIV infection, by vaccination may be detrimental and accelerate viral replication after HIV exposure. In the present study, we present a novel immunogen to selectively induce CD8(+) T cells but not CD4(+) T cells targeting viral antigens. The immunogen, CaV11, was constructed by tandem connection of overlapping 11-mer peptides spanning simian immunodeficiency virus (SIV) Gag capsid (CA) and Vif. Prime-boost immunization with DNA and Sendai virus (SeV) vectors expressing CaV11 efficiently induced Gag/Vif-specific CD8(+) T-cell responses with inefficient Gag/Vif-specific CD4(+) T-cell induction in rhesus macaques (n = 6). None of the macaques exhibited the enhancement of acute viral replication after an intravenous high-dose SIV challenge, which was observed in those immunized with DNA and SeV expressing the whole Gag protein in our previous study. Setpoint viral control post-infection was associated with SeV-specific CD4(+) T-cell responses post-immunization, suggesting contribution of SeV-specific helper responses to effective Gag/Vif-specific CD8(+) T-cell induction by vaccination. This immunogen design could be a promising method for selective induction of effective anti-HIV CD8(+) T-cell responses.Importance Induction of effective CD8(+) T-cell responses is an important HIV vaccine strategy. Several promising vaccine delivery tools have been developed, and immunogen optimization is now crucial for effective T-cell induction. Conventional immunogens have been designed to induce virus-specific CD4(+) T as well as CD8(+) T cells, but induction of virus-specific CD4(+) T cells that are preferential targets for HIV infection could enhance acute HIV proliferation. Here, we designed a novel immunogen to induce HIV-specific CD8(+) T cells without HIV-specific CD4(+) T-cell induction but with non-HIV antigen-specific CD4(+) T-cell help. Our analysis in a macaque AIDS model showed that our immunogen can efficiently elicit effective CD8(+) T but not CD4(+) T cells targeting viral antigens, resulting in no enhancement of acute viral replication after virus exposure. This immunogen design, also applicable for other currently-developed immunogens, could be a promising method for selective induction of effective anti-HIV CD8(+) T-cell responses.