title: 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 50microg 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-gamma 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.
authors.affiliation: Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA. Martha.Sedegah@med.navy.mil
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.forename: William O
authors.initials: WO
authors.lastname: Rogers
authors.forename: Maria
authors.initials: M
authors.lastname: Belmonte
authors.forename: Arnel
authors.initials: A
authors.lastname: Belmonte
authors.forename: Glenna
authors.initials: G
authors.lastname: Banania
authors.forename: Noelle B
authors.initials: NB
authors.lastname: Patterson
authors.forename: Denis
authors.initials: D
authors.lastname: Rusalov
authors.forename: Marilyn
authors.initials: M
authors.lastname: Ferrari
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D005260:Female; D007118:Immunoassay / Q000379:methods; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D010963:Plasmodium falciparum / Q000235:genetics; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010714:Phosphatidylethanolamines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C460866:vaxfectin