title: Immunization with apical membrane antigen 1 confers sterile infection-blocking immunity against Plasmodium sporozoite challenge in a rodent model.
abstract: Apical membrane antigen 1 (AMA-1) is a leading blood-stage malaria vaccine candidate. Consistent with a key role in erythrocytic invasion, AMA-1-specific antibodies have been implicated in AMA-1-induced protective immunity. AMA-1 is also expressed in sporozoites and in mature liver schizonts where it may be a target of protective cell-mediated immunity. Here, we demonstrate for the first time that immunization with AMA-1 can induce sterile infection-blocking immunity against Plasmodium sporozoite challenge in 80% of immunized mice. Significantly higher levels of gamma interferon (IFN-γ)/interleukin-2 (IL-2)/tumor necrosis factor (TNF) multifunctional T cells were noted in immunized mice than in control mice. We also report the first identification of minimal CD8(+) and CD4(+) T cell epitopes on Plasmodium yoelii AMA-1. These data establish AMA-1 as a target of both preerythrocytic- and erythrocytic-stage protective immune responses and validate vaccine approaches designed to induce both cellular and humoral immunity.
authors.affiliation: Queensland Institute of Medical Research, Infectious Diseases Programme, Herston, Queensland, Australia.
authors.forename: Sophie
authors.initials: S
authors.lastname: Schussek
authors.forename: Angela
authors.initials: A
authors.lastname: Trieu
authors.forename: Simon H
authors.initials: SH
authors.lastname: Apte
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia; D010967:Plasmodium yoelii; D015800:Protozoan Proteins / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D034101:Sporozoites / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium