T Cell Immunity Induced by Rhesus PD1-based DNA Vaccine Controls SHIV Infection in Rhesus Macaques

Abstract

Millions of people have died from AIDS worldwide and many more are currently living with HIV infection. An effective prophylactic HIV vaccine represents a solution to control the HIV/AIDS epidemic. Recently, we have developed a novel vaccine design by fusing an antigen of interest to a soluble programmed death-1 (PD-1) molecule. This vaccine design allows effective dendritic cell targeting and induction of strong T cell responses in mouse models. In this study, we developed and examined a new PD-1-based DNA vaccine in a rhesus macaque model of HIV infection. Our new DNA vaccine encodes a codon-optimized recombinant antigen consisting of a soluble rhesus macaque PD-1 fused to the simian immunodeficiency virus (SIV) Gag-p27 antigen. To assess its immunogenicity and efficacy, Chinese-origin rhesus macaques were immunized with the PD-1-based vaccine via intramuscular electroporation 3 times at 6-week intervals. The vaccine induced a Gag-specific antibody response. In addition, it elicited broad, poly-functional and long-lasting SIV-Gag-p27-specific CD4+ and CD8+ T cell responses. Interestingly, a T cell response specific to the SIV-Gag294-313 peptide was induced in 50% of the immunized macaques. This peptide is highly homologous to the immunodominant HIV-Gag293-312 epitope recognized by CD4+ T cells from HIV-infected elite controllers. More importantly, the vaccine induced protection against simian-human immunodeficiency virus challenge in all immunized macaques. In summary, the PD-1-based DNA vaccine elicits a protective Gag-specific immune response in rhesus macaques. This study suggests a potential use of the PD-1-based vaccine approach in HIV prevention.