Enhanced HIV-1 Gag-specific immunity induced by a sPD-1-based vaccine directed to dendritic cells

Abstract

HIV/AIDS is a serious disease worldwide. The development of a safe, effective and affordable HIV-1 vaccine remains the ultimate solution. This study is based on the discovery of a negative immune regulatory system, the PD-1/PD-L pathway, which exists on both human and other animals. The PD-1 ligands (PD-L1 and PD-L2) are expressed on DCs. So we hypothesize to utilize the soluble PD-1 parts to intervene in the negative signal transmission of the PD-1 pathway and to target the antigen to DCs as a mean to indentify vaccine strategy to enhance the virus specific immune responses. Here we constructed the novel vaccine and controls by inserting soluble PD-1 gene and/or HIV-1 p24 gene into the pVAX1 vector with fusing of rabbit Fc fragment named mspd1-p24-fc, and controls named mspd1-IgVΔ-p24-fc and p24-fc. When compared with control vaccines, we discovered that mspd1-p24fc can significantly enhance HIV-1 Gag-specific immune responses by measuring the number of IFN-γ expressed CD4 and CD8 T cells using Elispot assays and CD8 T cell tetramer staining. Furthermore, the mspd1-p24-fc can significantly enhance humoral immune responses by anti-Gag antibody titer analysis. Importantly, this novel vaccine protects mice against recombinant vaccinia virus-gagpol challenges. This novel vaccine design may be used as DNA vaccine model against other infectious disease and cancer which need eliciting significant antigen specific humoral and cellular immune responses.