title: Immunization of Aotus monkeys with a functional domain of the Plasmodium falciparum variant antigen induces protection against a lethal parasite line.
abstract: Immunity to Plasmodium falciparum in African children has been correlated with antibodies to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) variant gene family expressed on the surface of infected red cells. We immunized Aotus monkeys with a subregion of the Malayan Camp variant antigen (MCvar1) that mediates adhesion to the host receptor CD36 on the endothelial surface and present data that PfEMP1 is an important target for vaccine development. The immunization induced a high level of protection against the homologous strain. Protection correlated with the titer of agglutinating antibodies and occurred despite the expression of variant copies of the gene during recurrent waves of parasitemia. A second challenge with a different P. falciparum strain, to which there was no agglutinating activity, showed no protection but boosted the immune response to this region during the infection. The level of protection and the evidence of boosting during infection encourage further exploration of this concept for malaria vaccine development.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dbaruch@niaid.nih.gov
authors.forename: Dror I
authors.initials: DI
authors.lastname: Baruch
authors.forename: Benoit
authors.initials: B
authors.lastname: Gamain
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.forename: JoAnn S
authors.initials: JS
authors.lastname: Sullivan
authors.forename: Anthony
authors.initials: A
authors.lastname: Stowers
authors.forename: G Gale
authors.initials: GG
authors.lastname: Galland
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: William E
authors.initials: WE
authors.lastname: Collins
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D001029:Aotus trivirgatus / Q000276:immunology* / Q000469:parasitology*; D014644:Genetic Variation / Q000235:genetics*; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D009154:Mutation / Q000235:genetics; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines