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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification and Characterization of Functional Human Monoclonal Antibodies to Plasmodium vivax Duffy-Binding Protein

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Author(s):
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Carias, Lenore L. [1] ; Dechavanne, Sebastien [1] ; Nicolete, Vanessa C. [2] ; Sreng, Sokunthea [3] ; Suon, Seila [3] ; Amaratunga, Chanaki [4] ; Fairhurst, Rick M. [4] ; Dechavanne, Celia [1, 5] ; Barnes, Samantha [6] ; Witkowski, Benoit [7] ; Popovici, Jean [7] ; Roesch, Camille [7] ; Chen, Edwin [8, 9] ; Ferreira, Marcelo U. [2] ; Tolia, Niraj H. [8, 10] ; Adams, John H. [6] ; King, Christopher L. [1, 11]
Total Authors: 17
Affiliation:
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[1] Case Western Reserve Univ, Sch Med, Ctr Global Hlth & Dis, 10900 Euclid Ave, Cleveland, OH 44106 - USA
[2] Univ Sao Paulo, Dept Parasitol, BR-05508000 Sao Paulo - Brazil
[3] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh 12101 - Cambodia
[4] NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 - USA
[5] Paris Descartes Univ, French Natl Res Inst Dev, UMR Mother & Child Facing Trop Infect 261, F-75006 Paris - France
[6] Univ S Florida, Ctr Global Hlth & Infect Dis Res, Dept Global Hlth, Tampa, FL 33612 - USA
[7] Pasteur Inst Cambodia, Malaria Unit, Phnom Penh 12201 - Cambodia
[8] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 - USA
[9] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 - USA
[10] NIAID, Lab Malaria Immunol & Vaccinol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 - USA
[11] Cleveland VA Med Ctr, Cleveland, OH 44106 - USA
Total Affiliations: 11
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 202, n. 9, p. 2648-2660, MAY 1 2019.
Web of Science Citations: 4
Abstract

Plasmodium vivax invasion of reticulocytes relies on distinct receptor-ligand interactions between the parasite and host erythrocytes. Engagement of the highly polymorphic domain II of the P. vivax Duffy-binding protein (DBPII) with the erythrocyte's Duffy Ag receptor for chemokines (DARC) is essential. Some P vivax-exposed individuals acquired Abs to DBPII that block DBPIIDARC interaction and inhibit P vivax reticulocyte invasion, and Ab levels correlate with protection against P. vivax malaria. To better understand the functional characteristics and fine specificity of protective human Abs to DBPII, we sorted single DBPII-specific IgG(+) memory B cells from three individuals with high blocking activity to DBPII. We identified 12 DBPII-specific human mAbs from distinct lineages that blocked DBPII-DARC binding. All mAbs were P. vivax strain transcending and targeted known binding motifs of DBPII with DARC. Eleven mAbs competed with each other for binding, indicating recognition of the same or overlapping epitopes. Naturally acquired blocking Abs to DBPII from individuals with high levels residing in different P vivax- endemic areas worldwide competed with mAbs, suggesting broadly shared recognition sites. We also found that mAbs inhibited P. vivax entry into reticulocytes in vitro. These findings suggest that IgG(+) memory B cell activity in individuals with P vivax strain- transcending Abs to DBPII display a limited clonal response with inhibitory blocking directed against a distinct region of the molecule. (AU)

FAPESP's process: 09/52729-9 - Determinants and consequences of asymptomatic carriage of malaria parasites: population-based studies in rural Brazilian Amazonia
Grantee:Marcelo Urbano Ferreira
Support Opportunities: Regular Research Grants