Construction and immunogenicity of DNA vaccine plasmids encoding four Plasmodium vivax candidate vaccine antigens

Abstract

Plasmodium vivax is the second most common agent of human malaria. Although infection is rarely fatal, it nonetheless imposes a significant burden of illness in endemic areas. A successful vaccine against P. vivax will likely need to induce immune responses against both pre-erythrocytic and erythrocytic stage forms of the parasite. Accordingly, we constructed eight nucleic acid vaccines based on four antigens, the circumsporozoite protein (PvCSP) and sporozoite surface protein 2 (PvSSP2) from the pre-erythrocytic stage, and apical membrane antigen 1 (PvAMA1) and merozoite surface protein 1 (PvMSP1) from the erythrocytic stage. The constructs induced high levels of specific antibody in mice regardless of whether the antigen was expressed in native form or fused to a human tissue plasminogen activator leader peptide. High titer antibodies induced against PvCSP did not react with the protective AGDR epitope within the sequence of this antigen. These results support the immunogenicity of these four vaccine candidate antigens when delivered as nucleic acid vaccines.