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

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.
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Washington Univ. School of Medicine in St. Louis, St. Louis, MO (United States)
  2. Univ. of South Florida, Tampa, FL (United States)
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 22; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Univ. of California, Berkeley, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Duffy Binding Protein; Plasmodium vivax; broadly neutralizing; epitopes; malaria
OSTI Identifier:
1347692

Chen, Edwin, Salinas, Nichole D., Huang, Yining, Ntumngia, Francis, Plasencia, Manolo D., Gross, Michael L., Adams, John H., and Tolia, Niraj Harish. Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein. United States: N. p., Web. doi:10.1073/pnas.1600488113.
Chen, Edwin, Salinas, Nichole D., Huang, Yining, Ntumngia, Francis, Plasencia, Manolo D., Gross, Michael L., Adams, John H., & Tolia, Niraj Harish. Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein. United States. doi:10.1073/pnas.1600488113.
Chen, Edwin, Salinas, Nichole D., Huang, Yining, Ntumngia, Francis, Plasencia, Manolo D., Gross, Michael L., Adams, John H., and Tolia, Niraj Harish. 2016. "Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein". United States. doi:10.1073/pnas.1600488113. https://www.osti.gov/servlets/purl/1347692.
@article{osti_1347692,
title = {Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein},
author = {Chen, Edwin and Salinas, Nichole D. and Huang, Yining and Ntumngia, Francis and Plasencia, Manolo D. and Gross, Michael L. and Adams, John H. and Tolia, Niraj Harish},
abstractNote = {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.},
doi = {10.1073/pnas.1600488113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 22,
volume = 113,
place = {United States},
year = {2016},
month = {5}
}