title: Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection.
abstract: Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4(+), but not CD8(+), T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection.
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Leite
authors.affiliation: Department of Parasitology, University of São Paulo-USP, São Paulo, SP, Brazil.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Bargieri
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Bruna O
authors.initials: BO
authors.lastname: Carvalho
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil Instituto Carlos Chagas, Fundação Oswaldo Cruz-FIOCRUZ, Curitiba, PR, Brazil.
authors.forename: Letusa
authors.initials: L
authors.lastname: Albrecht
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz-FIOCRUZ, Manaus, AM, Brazil.
authors.forename: Stefanie C P
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Ana Carolina A V
authors.initials: AC
authors.lastname: Kayano
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Alessandro S
authors.initials: AS
authors.lastname: Farias
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Wan Ni
authors.initials: WN
authors.lastname: Chia
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Bruce
authors.initials: B
authors.lastname: Russell
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Catarina
authors.initials: C
authors.lastname: Castiñeiras
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Leonilda M B
authors.initials: LM
authors.lastname: Santos
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Brocchi
authors.affiliation: Department of Parasitology, University of São Paulo-USP, São Paulo, SP, Brazil.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wunderlich
authors.affiliation: Department of Clinical and Toxicological Analysis, Pharmaceutical Sciences, University of São Paulo-USP, São Paulo, SP, Brazil.
authors.forename: Irene S
authors.initials: IS
authors.lastname: Soares
authors.affiliation: Center for Cellular and Molecular Therapy-CTCMol, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Department of Genetics, Evolution and Bioagents, University of Campinas-UNICAMP, Campinas, SP, Brazil fabiotmc72@gmail.com.
authors.forename: Fabio T M
authors.initials: FT
authors.lastname: Costa
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007114:Immunization; D008288:Malaria / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008297:Male; D052940:Merozoites / Q000737:chemistry / Q000254:growth & development / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D034101:Sporozoites / Q000737:chemistry / Q000254:growth & development / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins