title: Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein.
abstract: Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain-specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP-based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
authors.forename: Edwin
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
authors.forename: Nichole D
authors.initials: ND
authors.lastname: Salinas
authors.affiliation: Department of Chemistry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Global Health Infectious Disease Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620;
authors.forename: Francis
authors.initials: F
authors.lastname: Ntumngia
authors.affiliation: Department of Chemistry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
authors.forename: Manolo D
authors.initials: MD
authors.lastname: Plasencia
authors.affiliation: Department of Chemistry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gross
authors.affiliation: Global Health Infectious Disease Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620;
authors.forename: John H
authors.initials: JH
authors.lastname: Adams
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110 tolia@wustl.edu.
authors.forename: Niraj Harish
authors.initials: NH
authors.lastname: Tolia
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014644:Genetic Variation; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016780:Malaria, Vivax / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008958:Models, Molecular; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D018985:Epitopes, B-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface
keywords: Duffy Binding Protein; Plasmodium vivax; broadly neutralizing; epitopes; malaria