Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.

Glycan masking is an emerging vaccine design strategy to focus antibody responses to specific epitopes, but it has mostly been evaluated on the already heavily glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to investigate the binding interaction of Plasmodium vivax Duffy B...

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Autores principales:	Sowmya Sampath, Chris Carrico, Joel Janes, Sairam Gurumoorthy, Claire Gibson, Martin Melcher, Chetan E Chitnis, Ruobing Wang, William R Schief, Joseph D Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/14ff8003af05497592930148dcb25170
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spelling	oai:doaj.org-article:14ff8003af05497592930148dcb251702021-11-18T06:05:31ZGlycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.1553-73661553-737410.1371/journal.ppat.1003420https://doaj.org/article/14ff8003af05497592930148dcb251702013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853575/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Glycan masking is an emerging vaccine design strategy to focus antibody responses to specific epitopes, but it has mostly been evaluated on the already heavily glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to investigate the binding interaction of Plasmodium vivax Duffy Binding Protein (PvDBP) and the Duffy Antigen Receptor for Chemokines (DARC) and to evaluate if glycan-masked PvDBPII immunogens would focus the antibody response on key interaction surfaces. Four variants of PVDBPII were generated and probed for function and immunogenicity. Whereas two PvDBPII glycosylation variants with increased glycan surface coverage distant from predicted interaction sites had equivalent binding activity to wild-type protein, one of them elicited slightly better DARC-binding-inhibitory activity than wild-type immunogen. Conversely, the addition of an N-glycosylation site adjacent to a predicted PvDBP interaction site both abolished its interaction with DARC and resulted in weaker inhibitory antibody responses. PvDBP is composed of three subdomains and is thought to function as a dimer; a meta-analysis of published PvDBP mutants and the new DBPII glycosylation variants indicates that critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. Our findings suggest that DARC-binding-inhibitory antibody epitope(s) lie close to the predicted DARC interaction site, and that addition of N-glycan sites distant from this site may augment inhibitory antibodies. Thus, glycan resurfacing is an attractive and feasible tool to investigate protein structure-function, and glycan-masked PvDBPII immunogens might contribute to P. vivax vaccine development.Sowmya SampathChris CarricoJoel JanesSairam GurumoorthyClaire GibsonMartin MelcherChetan E ChitnisRuobing WangWilliam R SchiefJoseph D SmithPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 6, p e1003420 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sowmya Sampath Chris Carrico Joel Janes Sairam Gurumoorthy Claire Gibson Martin Melcher Chetan E Chitnis Ruobing Wang William R Schief Joseph D Smith Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
description	Glycan masking is an emerging vaccine design strategy to focus antibody responses to specific epitopes, but it has mostly been evaluated on the already heavily glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to investigate the binding interaction of Plasmodium vivax Duffy Binding Protein (PvDBP) and the Duffy Antigen Receptor for Chemokines (DARC) and to evaluate if glycan-masked PvDBPII immunogens would focus the antibody response on key interaction surfaces. Four variants of PVDBPII were generated and probed for function and immunogenicity. Whereas two PvDBPII glycosylation variants with increased glycan surface coverage distant from predicted interaction sites had equivalent binding activity to wild-type protein, one of them elicited slightly better DARC-binding-inhibitory activity than wild-type immunogen. Conversely, the addition of an N-glycosylation site adjacent to a predicted PvDBP interaction site both abolished its interaction with DARC and resulted in weaker inhibitory antibody responses. PvDBP is composed of three subdomains and is thought to function as a dimer; a meta-analysis of published PvDBP mutants and the new DBPII glycosylation variants indicates that critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. Our findings suggest that DARC-binding-inhibitory antibody epitope(s) lie close to the predicted DARC interaction site, and that addition of N-glycan sites distant from this site may augment inhibitory antibodies. Thus, glycan resurfacing is an attractive and feasible tool to investigate protein structure-function, and glycan-masked PvDBPII immunogens might contribute to P. vivax vaccine development.
format	article
author	Sowmya Sampath Chris Carrico Joel Janes Sairam Gurumoorthy Claire Gibson Martin Melcher Chetan E Chitnis Ruobing Wang William R Schief Joseph D Smith
author_facet	Sowmya Sampath Chris Carrico Joel Janes Sairam Gurumoorthy Claire Gibson Martin Melcher Chetan E Chitnis Ruobing Wang William R Schief Joseph D Smith
author_sort	Sowmya Sampath
title	Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
title_short	Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
title_full	Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
title_fullStr	Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
title_full_unstemmed	Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.
title_sort	glycan masking of plasmodium vivax duffy binding protein for probing protein binding function and vaccine development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/14ff8003af05497592930148dcb25170
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Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.

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