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.