title: Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates.
abstract: BACKGROUND
  Despite years of effort, a licensed malaria vaccine is not yet available. One of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. To counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. Since most of the malaria vaccine antigens that have been evaluated in people have not elicited a protective immune response, there is a need to identify additional protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria antigens was evaluated in a Plasmodium yoelii/mouse protection model.
  
  
  METHODS
  Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one, two or all three P. yoelii vaccine antigens. The immunized mice were challenged with 300 P. yoelii sporozoites and evaluated for subsequent infection.
  
  
  RESULTS
  Vaccines that expressed any one of the three antigens did not protect a high percentage of mice against a P. yoelii challenge. However, vaccines that expressed all three antigens protected a higher percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection was primarily associated with two of the three P. yoelii antigens. The protection elicited by a vaccine expressing these two antigens exceeded the sum of the protection elicited by the single antigen vaccines, suggesting a potential synergistic interaction.
  
  
  CONCLUSIONS
  This work identifies two promising malaria vaccine antigen candidates and suggests that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.
authors.affiliation: US Military Malaria Vaccine Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, USA. keith.limbach@med.navy.mil
authors.forename: Keith
authors.initials: K
authors.lastname: Limbach
authors.forename: Joao
authors.initials: J
authors.lastname: Aguiar
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gowda
authors.forename: Noelle
authors.initials: N
authors.lastname: Patterson
authors.forename: Esteban
authors.initials: E
authors.lastname: Abot
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.forename: John
authors.initials: J
authors.lastname: Sacci
authors.forename: Thomas
authors.initials: T
authors.lastname: Richie
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012376:Rodent Diseases / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D019444:Vaccines, DNA