A D-peptide-based HIV gelatinous combination vaccine improves therapy in ART-delayed macaques of chronic infection

Abstract

Improving virus control in HIV-infected individuals without a timely antiretroviral therapy (ART) intervention still remains an important challenge, which is largely due to the lack of a potent means to co-deliver a complex therapeutic system consisting of diverse types of vaccines and drugs to the human body. Here, we used a one-step method to rapidly construct a new D-peptide-based gelatinous combination vaccine (GCV), which possesses a potent loading capacity for diverse types of antigens and a sustainable release profile, and exhibits efficient internalization by dendritic cells (DCs). As a novel immunization strategy, GCV can efficiently co-deliver two critical HIV antigens (Env and Gag) in combination with a potent immunostimulator, interleukin 21 (IL-21), in a controllable and balanced manner to induce a high-quality immune response against HIV chronic infection in non-human primates. In SHIV-SF162P3-challenged rhesus macaques initiating ART at week 8 of infection (a chronic infection model), GCV simultaneously activated the critical polyfunctional CD4+ and CD8+ T cell response which has never been reported in existing vaccination strategies. More importantly, GCV elicited a persistent suppression against viral loads (10–100 fold) and viral rebound, as well as eliminated the viral reservoir following ART discontinuation. These findings describe a new and promising therapeutic vaccine candidate for realizing a functional cure against chronic HIV infection.