Vaxfectin ® enhances both antibody and in vitro T cell responses to each component of a 5-gene Plasmodium falciparum plasmid DNA vaccine mixture administered at low doses

Abstract

We previously reported the capacity of the cationic lipid-based formulation, Vaxfectin ®, to enhance the immunogenicity and protective efficacy of a low dose plasmid DNA vaccine against Plasmodium yoelii malaria in mice. Here, we have extended this finding to human Plasmodium falciparum genes, evaluating the immune enhancing effect of Vaxfectin ® formulation on a mixture, designated CSLAM, of five plasmid DNA vaccines encoding antigens from the sporozoite ( PfCSP, PfSSP2/TRAP), intrahepatic ( PfLSA1), and erythrocytic ( PfAMA1, PfMSP1) life cycle stages of P. falciparum administered at 2, 10 or 50 μg doses. Vaxfectin ® formulation enhanced both antibody and cellular immune responses to each component of the multi-antigen vaccine mixture, as assessed by ELISA, IFAT, and IFN-γ ELIspot, respectively. There was no apparent antigenic competition, as indicated by comparison of responses induced in mice immunized with PfCSP vs. CSLAM. These data showing that Vaxfectin ® can enhance the immunogenicity of plasmid DNA vaccines administered at low doses per body weight, and in combinations, has important clinical implications for the development of a vaccine against malaria, as well as against other public health threats.