title: Human antibodies against Plasmodium falciparum liver-stage antigen 3 cross-react with Plasmodium yoelii preerythrocytic-stage epitopes and inhibit sporozoite invasion in vitro and in vivo.
abstract: The Plasmodium falciparum liver-stage antigen 3 (LSA3), a recently identified preerythrocytic antigen, induces protection against malaria in chimpanzees. Using antibodies from individuals with hyperimmunity to malaria affinity purified on recombinant or synthetic polypeptides of LSA3, we identified four non-cross-reactive B-cell epitopes in Plasmodium yoelii preerythrocytic stages. On sporozoites the P. yoelii protein detected has a molecular mass similar to that of LSA3. T-cell epitopes cross-reacting with P. yoelii were also demonstrated using peripheral blood lymphocytes from LSA3-immunized chimpanzees. In contrast, no cross-reactive epitopes were found in Plasmodium berghei. LSA3-specific human antibodies exerted up to 100% inhibition of in vitro invasion of P. yoelii sporozoites into mouse hepatocytes. This strong in vitro activity was reproduced in vivo by passive transfer of LSA3 antibodies. These results indicate that the homologous epitopes may be biologically functional and suggest that P. yoelii could be used as a model to assess the antisporozoite activity of anti-LSA3 antibodies.
authors.affiliation: Laboratoire de Parasitologie Biomédicale, Institut Pasteur, 75015 Paris Cedex 15, France.
authors.forename: K
authors.initials: K
authors.lastname: Brahimi
authors.forename: E
authors.initials: E
authors.lastname: Badell
authors.forename: J P
authors.initials: JP
authors.lastname: Sauzet
authors.forename: L
authors.initials: L
authors.lastname: BenMohamed
authors.forename: P
authors.initials: P
authors.lastname: Daubersies
authors.forename: C
authors.initials: C
authors.lastname: Guérin-Marchand
authors.forename: G
authors.initials: G
authors.lastname: Snounou
authors.forename: P
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D002679:Pan troglodytes; D010963:Plasmodium falciparum / Q000276:immunology*; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D011994:Recombinant Proteins; C067302:liver stage-specific antigen, Plasmodium