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


ABSTRACT: 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. 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.

SUBMITTER: Chen E 

PROVIDER: S-EPMC4896725 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Chen Edwin E   Salinas Nichole D ND   Huang Yining Y   Ntumngia Francis F   Plasencia Manolo D MD   Gross Michael L ML   Adams John H JH   Tolia Niraj Harish NH  

Proceedings of the National Academy of Sciences of the United States of America 20160518 22


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,  ...[more]

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