title: Strain-Transcending Inhibitory Antibodies against Homologous and Heterologous Strains of Duffy Binding Protein region II.
abstract: Duffy binding protein region II (DBPII) is a promising vaccine candidate against vivax malaria. However, polymorphisms of DBPII are the major obstacle to designing a successful vaccine. Here, we examined whether anti-DBPII antibodies from individual P. vivax exposures provide strain-transcending immunity and whether their presence is associated with DBPII haplotypes found in patients with acute P. vivax. The ability of antibodies to inhibit DBL-TH-erythrocyte binding was tested by COS7 erythrocyte binding inhibition assay. Seven samples of high responders (HR) were identified from screening anti-DBPII levels. HR no.3 and HR no.6 highly inhibited all DBL-TH binding to erythrocytes, by >80%. Antibodies from these two patients' plasma had the potential to be broadly inhibitory against DBL-TH1, -TH2, -TH6, -TH7, -TH8 and -TH9 haplotypes when plasma was serially diluted from 1:500 to 1:2000. To further examine the association of DBPII haplotypes and the ability of antibodies to broadly inhibit DBL-TH variants, the individual samples underwent sequencing analysis and the inhibitory function of the anti-DBPII antibodies was tested. The patterns of DBPII polymorphisms in acute patients were classified into two groups, DBPII Sal I (55%) and DBL-TH variants (45%). Plasma from Sal I and DBPII-TH patients who had the highest inhibition against Sal I or DBL-TH4 and -TH5 was serially diluted from 1:500 to 1:2000 and their inhibitory capacity was tested against a panel of DBL-TH haplotypes. Results provided evidence of both strain-transcending inhibition as well as strain-specific inhibition by antibodies that blocked erythrocyte binding against some DBL-TH variants and against homologous alleles. This study demonstrated broad inhibition by anti-DBPII antibodies against DBL-TH haplotypes in natural P. vivax exposed individuals. The identification of conserved epitopes among DBL-TH may have implications for vaccine development of a DBPII-based vaccine against diverse P. vivax infections.
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
authors.forename: Sudarat
authors.initials: S
authors.lastname: Wongkidakarn
authors.affiliation: Department of Biology, Southwestern Adventist University, Keene, Texas, United States of America.
authors.forename: Amy M
authors.initials: AM
authors.lastname: McHenry
authors.affiliation: Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.affiliation: Department of Global Health, University of South Florida, Tampa, Florida, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Adams
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
authors.forename: Patchanee
authors.initials: P
authors.lastname: Chootong
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control; D010966:Plasmodium vivax / Q000145:classification / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D013785:Thailand
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins