PD-1 blockade enhances HIV-1 vaccine-induced CD8+ T-cell responses in PWH early ART-treated

Abstract

Current HIV-1 therapeutic vaccines do not generate T-cell immune responses in people with HIV-1 (PWH) able to eradicate the virus or to broadly control viral replication. The expression of inhibitory receptors (IRs) may limit vaccine efficacy by reducing specific effector functions in vaccine-induced T-cells. Recently, the clinical use of antibodies targeting IRs or immune checkpoint blockade (ICB) has demonstrated remarkable success in cancer remission. Therefore, there is a potential benefit of using ICB in PWH to improve the effectiveness of vaccine-induced T-cell responses. Here, we evaluated functional changes in vaccine-induced HIV-specific CD8 T-cell responses by in-vitro PD-1 and TIM-3 blockade during immune stimulation in PWH early ART-treated and vaccinated (Etvac). We compared Etvac to PWH early ART-treated (Et) and chronic ART-treated PWH (Chro). Our results demonstrate a significant increase in the functional responses of vaccine-induced HIV-1-specific CD8 T-cells upon PD-1 but not TIM-3 blockade in cellular proliferation, IFN{gamma} production, and activation. Although no effect was found in Et, similar findings were obtained in HIV-1-specific CD8 T-cells in Chro for combined PD-1/TIM-3 blockade. Moreover, we identify in Etvac a direct association between PD-1 expression in CD8+ T cells and in vitro response to anti-PD-1 treatment. Our findings support the potential adjuvant effect of PD-1 blockade to improve HIV-1 therapeutic vaccine efficacy in early ART-treated PWH for future human studies.