title: Plasmodium vivax apical membrane antigen-1: comparative recognition of different domains by antibodies induced during natural human infection.
abstract: The Apical Membrane Antigen-1 (AMA-1) of Plasmodium sp. has been suggested as a vaccine candidate against malaria. This protein seems to be involved in merozoite invasion and its extra-cellular portion contains three distinct domains: DI, DII, and DIII. Previously, we described that Plasmodium vivax AMA-1 (PvAMA-1) ectodomain is highly immunogenic in natural human infections. Here, we expressed each domain, separately or in combination (DI-II or DII-III), as bacterial recombinant proteins to map immunodominant epitopes within the PvAMA-1 ectodomain. IgG recognition was assessed by ELISA using sera of P. vivax-infected individuals collected from endemic regions of Brazil or antibodies raised in immunized mice. The frequencies of responders to recombinant proteins containing the DII were higher than the others and similar to the ones observed against the PvAMA-1 ectodomain. Moreover, ELISA inhibition assays using the PvAMA-1 ectodomain as substrate revealed the presence of many common epitopes within DI-II that are recognized by human immune antibodies. Finally, immunization of mice with the PvAMA-1 ectodomain induced high levels of antibodies predominantly to DI-II. Together, our results indicate that DII is particularly immunogenic during natural human infections, thus indicating that this region could be used as part of an experimental sub-unit vaccine to prevent vivax malaria.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Prof. Lineu Prestes, 580, Cidade Universitária, 05508-900, São Paulo, SP, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Múfalo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gentil
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Bargieri
authors.forename: Fabio T M
authors.initials: FT
authors.lastname: Costa
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: Irene S
authors.initials: IS
authors.lastname: Soares
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016780:Malaria, Vivax / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007106:Immune Sera; D007074:Immunoglobulin G; D008565:Membrane Proteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; C090077:apical membrane antigen I, Plasmodium