title: Natural acquired inhibitory antibodies to Plasmodium vivax Duffy binding protein (PvDBP-II) equally block erythrocyte binding of homologous and heterologous expressed PvDBP-II on the surface of COS-7 cells.
abstract: The binding domain of Plasmodium vivax Duffy binding protein (PvDBP-II) is a promising blood-stage vaccine candidate for vivax malaria. For the development of a successful vivax malaria vaccine based on DBP-II, the antigenic diversity and also naturally occurring functional antibodies to different PvDBP-II variant types in the various populations must be determined. However, similar to other blood-stage antigens, allelic variation within the PvDBP-II is a fundamental challenge for the development of a broadly efficient vaccine. The present study was performed to define whether the polymorphisms in PvDBP-II influence the nature of functional inhibitory activity of naturally acquired or induced anti-DBP-II antibodies in mice. In this investigation, five genetically distinct variants of PvDBP-II were transiently expressed on the COS-7 cell surface. Erythrocyte-binding inhibition assay (EBIA) was performed using human sera infected with corresponding and non-corresponding P. vivax variants as well as by the use of mice sera immunized with different expressed recombinant PvDBP-IIs. EBIA results showed that the inhibitory percentage varied between 50 and 63 % by using sera from infected individuals, and in case of mouse antisera, inhibition was in the range of 76-86 %. Interestingly, no significant difference was detected in red blood cell binding inhibition when different PvDBP-II variants on the COS-7 cell surfaces were incubated with heterologous and homologous sera infected with PvDBP-II variants. This suggests that the detected polymorphisms in all five forms of PvDBP-II may not affect functional activity of anti-DBP-II antibodies. In conclusion, our results revealed that there are functional cross-reactive antibody responses to heterologous PvDBP-II variants that might provide a broader inhibitory response against all, or at least the majority of strains compared to single allele of this protein that should be considered in development of PvDBP-II-based vaccine.
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Vahideh
authors.initials: V
authors.lastname: Valizadeh
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran. zakerimvrg@gmail.com.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Zakeri
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Akram A
authors.initials: AA
authors.lastname: Mehrizi
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Mirkazemi
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Navid D
authors.initials: ND
authors.lastname: Djadid
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002648:Child; D004847:Epithelial Cells / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface
keywords: Duffy binding protein; Functional antibodies; Plasmodium vivax; Vaccine