A Novel Immunogen Selectively Eliciting CD8 ⁺ T Cells but Not CD4 ⁺ T Cells Targeting Immunodeficiency Virus Antigens

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 cells 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.