Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection

King, CL; Michon, P; Shakri, AR; Marcotty, A; Stanisic, D; Zimmerman, PA; Cole-Tobian, JL; Mueller, I; Chitnis, CE

Author(s): King, CL; Michon, P; Shakri, AR; Marcotty, A; Stanisic, D; Zimmerman, PA; Cole-Tobian, JL; Mueller, I; Chitnis, CE;
Details: Publication Year 2008-06-17,Volume 105,Issue #24,Page 8363-8368
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: Individuals residing in malaria-endemic regions acquire protective immunity after repeated infection with malaria parasites; however, mechanisms of protective immunity and their immune. correlates are poorly understood. Blood-stage infection with Plasmodium vivax depends completely on interaction of P. vivax Duffy-binding protein (PvDBP) with the Duffy antigen on host erythrocytes. Here, we performed a prospective cohort treatment/reinfection study of children (5-14 years) residing in a P. vivax-endemic region of Papua New Guinea (PNG) in which children were cleared of blood-stage infection and then examined biweekly for reinfection for 25 weeks. To test the hypothesis that naturally acquired binding inhibitory antibodies (BI-Abs) targeting PvDBP region II (PvDBPII) provide protection against P. vivax infection, we used a quantitative receptor-binding assay to distinguish between antibodies that merely recognize PvDBP and those that inhibit binding to Duffy. The presence of high-level BIAbs (> 90% inhibition of PvDBPII-Duffy binding, n = 18) before treatment was associated with delayed time to P. vivax reinfection diagnosed by light microscopy (P = 0.02), 55% reduced risk of P. vivax reinfection (Hazard's ratio = 0.45, P = 0.04), and 48% reduction in geometric mean A vivax parasitemia (P < 0.001) when compared with children with low-level BIAbs (n = 148). Further, we found that stable, high-level BIAbs displayed strain-transcending inhibition by reducing reinfection with similar efficiency of PING P. vivax strains characterized by six diverse PvDBPII haplotypes. These observations demonstrate a functional correlate of protective immunity in vivo and provide support for developing a vaccine against P. vivax malaria based on PvDBPII.
Publisher: NATL ACAD SCIENCES
Keywords: NEW-GUINEAN CHILDREN; MALARIA PARASITES; KNOWLESI; IDENTIFICATION; FALCIPARUM; RESIDUES; INVASION; DOMAIN; ASSAY; POLYMORPHISMS
Publisher's Version: https://doi.org/10.1073/pnas.0800371105
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-06-17 12:00:00