Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

Chen, Edwin; Salinas, Nichole D.; Huang, Yining; Ntumngia, Francis; Plasencia, Manolo D.; Gross, Michael L.; Adams, John H.; Tolia, Niraj Harish

doi:10.1073/pnas.1600488113

Title: Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

Journal Article · Wed May 18 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1600488113· OSTI ID:1347692

Chen, Edwin ^[1]; Salinas, Nichole D. ^[1]; Huang, Yining ^[1]; Ntumngia, Francis ^[2]; Plasencia, Manolo D. ^[1]; Gross, Michael L. ^[1]; Adams, John H. ^[2]; Tolia, Niraj Harish ^[1]

Washington Univ. School of Medicine in St. Louis, St. Louis, MO (United States)
Univ. of South Florida, Tampa, FL (United States)

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. In conclusion, 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.

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Research Organization:: Univ. of California, Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1347692

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 22; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 71 works

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Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA Mitran, Catherine J.; Mena, Angie; Gnidehou, Sedami mBio, Vol. 10, Issue 5 https://doi.org/10.1128/mbio.02343-19	journal	October 2019
Development of Blood Stage Malaria Vaccines Vijayan, Aneesh; Chitnis, Chetan E. Methods in Molecular Biology https://doi.org/10.1007/978-1-4939-9550-9_15	book	January 2019
Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry Benhaim, Mark; Lee, Kelly K.; Guttman, Miklos Protein & Peptide Letters, Vol. 26, Issue 1 https://doi.org/10.2174/0929866526666181212165037	journal	February 2019

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59 BASIC BIOLOGICAL SCIENCES
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broadly neutralizing
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