Cargando…

Heterotypic interactions drive antibody synergy against a malaria vaccine candidate

Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candid...

Descripción completa

Detalles Bibliográficos
Autores principales: Ragotte, Robert J., Pulido, David, Lias, Amelia M., Quinkert, Doris, Alanine, Daniel G. W., Jamwal, Abhishek, Davies, Hannah, Nacer, Adéla, Lowe, Edward D., Grime, Geoffrey W., Illingworth, Joseph J., Donat, Robert F., Garman, Elspeth F., Bowyer, Paul W., Higgins, Matthew K., Draper, Simon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854392/
https://www.ncbi.nlm.nih.gov/pubmed/35177602
http://dx.doi.org/10.1038/s41467-022-28601-4
_version_ 1784653434339721216
author Ragotte, Robert J.
Pulido, David
Lias, Amelia M.
Quinkert, Doris
Alanine, Daniel G. W.
Jamwal, Abhishek
Davies, Hannah
Nacer, Adéla
Lowe, Edward D.
Grime, Geoffrey W.
Illingworth, Joseph J.
Donat, Robert F.
Garman, Elspeth F.
Bowyer, Paul W.
Higgins, Matthew K.
Draper, Simon J.
author_facet Ragotte, Robert J.
Pulido, David
Lias, Amelia M.
Quinkert, Doris
Alanine, Daniel G. W.
Jamwal, Abhishek
Davies, Hannah
Nacer, Adéla
Lowe, Edward D.
Grime, Geoffrey W.
Illingworth, Joseph J.
Donat, Robert F.
Garman, Elspeth F.
Bowyer, Paul W.
Higgins, Matthew K.
Draper, Simon J.
author_sort Ragotte, Robert J.
collection PubMed
description Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.
format Online
Article
Text
id pubmed-8854392
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-88543922022-03-04 Heterotypic interactions drive antibody synergy against a malaria vaccine candidate Ragotte, Robert J. Pulido, David Lias, Amelia M. Quinkert, Doris Alanine, Daniel G. W. Jamwal, Abhishek Davies, Hannah Nacer, Adéla Lowe, Edward D. Grime, Geoffrey W. Illingworth, Joseph J. Donat, Robert F. Garman, Elspeth F. Bowyer, Paul W. Higgins, Matthew K. Draper, Simon J. Nat Commun Article Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets. Nature Publishing Group UK 2022-02-17 /pmc/articles/PMC8854392/ /pubmed/35177602 http://dx.doi.org/10.1038/s41467-022-28601-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ragotte, Robert J.
Pulido, David
Lias, Amelia M.
Quinkert, Doris
Alanine, Daniel G. W.
Jamwal, Abhishek
Davies, Hannah
Nacer, Adéla
Lowe, Edward D.
Grime, Geoffrey W.
Illingworth, Joseph J.
Donat, Robert F.
Garman, Elspeth F.
Bowyer, Paul W.
Higgins, Matthew K.
Draper, Simon J.
Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title_full Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title_fullStr Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title_full_unstemmed Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title_short Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
title_sort heterotypic interactions drive antibody synergy against a malaria vaccine candidate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854392/
https://www.ncbi.nlm.nih.gov/pubmed/35177602
http://dx.doi.org/10.1038/s41467-022-28601-4
work_keys_str_mv AT ragotterobertj heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT pulidodavid heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT liasameliam heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT quinkertdoris heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT alaninedanielgw heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT jamwalabhishek heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT davieshannah heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT naceradela heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT loweedwardd heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT grimegeoffreyw heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT illingworthjosephj heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT donatrobertf heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT garmanelspethf heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT bowyerpaulw heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT higginsmatthewk heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate
AT drapersimonj heterotypicinteractionsdriveantibodysynergyagainstamalariavaccinecandidate