Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine

Abstract Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of...

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Main Authors: Daniel O’Connor, Elizabeth A. Clutterbuck, Malick M. Gibani, Sagida Bibi, Katherine A. Sanders, Rebecca Makinson, Dominic F. Kelly, Andrew J. Pollard
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61571-x
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author Daniel O’Connor
Elizabeth A. Clutterbuck
Malick M. Gibani
Sagida Bibi
Katherine A. Sanders
Rebecca Makinson
Dominic F. Kelly
Andrew J. Pollard
author_facet Daniel O’Connor
Elizabeth A. Clutterbuck
Malick M. Gibani
Sagida Bibi
Katherine A. Sanders
Rebecca Makinson
Dominic F. Kelly
Andrew J. Pollard
author_sort Daniel O’Connor
collection DOAJ
description Abstract Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of protection for recent vaccine licensures. Using advanced cellular and transcriptomic analyses, we examined B cell responses to the Ad26.ZEBOV, MVA-BN-Filo EVD vaccine. Our findings reveal robust plasma cell and lasting B cell memory responses post-vaccination. Machine-learning models trained on blood gene expression predicted antibody response magnitude. Notably, we identified a unique B cell receptor CDRH3 sequence post-vaccination resembling known Orthoebolavirus zairense (EBOV) glycoprotein-binding antibodies. Single-cell analyses further detailed changes in plasma cell frequency, subclass usage, and CDRH3 properties. These results highlight the predictive power of early immune responses, captured through systems immunology, in shaping vaccine-induced B cell immunity.
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spelling doaj-art-2efe053004e049d7a089a81f9f8c9fc02025-08-20T04:02:56ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61571-xPrediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccineDaniel O’Connor0Elizabeth A. Clutterbuck1Malick M. Gibani2Sagida Bibi3Katherine A. Sanders4Rebecca Makinson5Dominic F. Kelly6Andrew J. Pollard7Oxford Vaccine Group, Department of Paediatrics, University of OxfordOxford Vaccine Group, Department of Paediatrics, University of OxfordDepartment of Infectious Disease, Imperial College London, St Mary’s CampusOxford Vaccine Group, Department of Paediatrics, University of OxfordOxford Vaccine Group, Department of Paediatrics, University of OxfordNIHR Oxford Biomedical Research CentreOxford Vaccine Group, Department of Paediatrics, University of OxfordOxford Vaccine Group, Department of Paediatrics, University of OxfordAbstract Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of protection for recent vaccine licensures. Using advanced cellular and transcriptomic analyses, we examined B cell responses to the Ad26.ZEBOV, MVA-BN-Filo EVD vaccine. Our findings reveal robust plasma cell and lasting B cell memory responses post-vaccination. Machine-learning models trained on blood gene expression predicted antibody response magnitude. Notably, we identified a unique B cell receptor CDRH3 sequence post-vaccination resembling known Orthoebolavirus zairense (EBOV) glycoprotein-binding antibodies. Single-cell analyses further detailed changes in plasma cell frequency, subclass usage, and CDRH3 properties. These results highlight the predictive power of early immune responses, captured through systems immunology, in shaping vaccine-induced B cell immunity.https://doi.org/10.1038/s41467-025-61571-x
spellingShingle Daniel O’Connor
Elizabeth A. Clutterbuck
Malick M. Gibani
Sagida Bibi
Katherine A. Sanders
Rebecca Makinson
Dominic F. Kelly
Andrew J. Pollard
Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
Nature Communications
title Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
title_full Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
title_fullStr Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
title_full_unstemmed Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
title_short Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine
title_sort prediction and characterisation of the human b cell response to a heterologous two dose ebola vaccine
url https://doi.org/10.1038/s41467-025-61571-x
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