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 |
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Authors: | Martha Sedegah William O. Rogers Maria Belmonte Arnel Belmonte Glenna Banania Noelle B. Patterson Denis Rusalov Marilyn Ferrari Thomas L. Richie Denise L. Doolan |
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Affiliation: | 1. Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA;2. Vical Inc., 10390 Pacific Center Court, San Diego, CA 92121-4340, USA |
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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. |
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Keywords: | APCs, antigen presenting cells CI, confidence interval D-D, DNA&ndash DNA immunization regimen D-V, DNA-recombinant viral boost immunization regimen ELISA, enzyme-linked immunosorbent assay ELISpot, enzyme-linked immunospot IFA, immunofluorescent antibody test IFN-γ, interferon-gamma pDNA, plasmid DNA Pf, Plasmodium falciparum CSP, circumsporozoite protein SSP2, sporozoite surface protein 2 LSA1, liver stage antigen-1 AMA1, apical merozoite antigen-1 MSP142 {3D7 strain}, merozoite surface protein-1 SFC, spot-forming cells |
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