Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Stewart, A. et al. (2022) Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus. Frontiers in Immunology, 13, 807104. (doi: 10.3389/fimmu.2022.807104) (PMID:35592326) (PMCID:PMC9111746)

Abstract

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.

• Item Type: Articles
• Keywords: Immunology, B cell, COVID-19, ebola, RSV (respiratory syncytial virus), immunity, repertoire, class-switch recombination (CSR).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Scott, Dr Janet
• Authors: Stewart, A., Sinclair, E., Ng, J. C.-F., O’Hare, J. S., Page, A., Serangeli, I., Margreitter, C., Orsenigo, F., Longman, K., Frampas, C., Costa, C., Lewis, H.-M., Kasar, N., Wu, B., Kipling, D., Openshaw, P. J., Chiu, C., Baillie, J. K., Scott, J. T., Semple, M. G., Bailey, M. J., Fraternali, F., and Dunn-Walters, D. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Frontiers in Immunology
• Publisher: Frontiers Media
• ISSN: 1664-3224
• ISSN (Online): 1664-3224
• Copyright Holders: Copyright © 2022 Stewart, Sinclair, Ng, O’Hare, Page, Serangeli, Margreitter, Orsenigo, Longman, Frampas, Costa, Lewis, Kasar, Wu, Kipling, Openshaw, Chiu, Baillie, Scott, Semple, Bailey, Fraternali and Dunn-Walters
• First Published: First published in Frontiers in Immunology 13: 807104
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.5281/zenodo.5146019

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173707		Institutional Strategic Support Fund (2016)	Anna Dominiczak	Wellcome Trust (WELLCOTR)	204820/Z/16/Z	Institute of Cardiovascular & Medical Sciences