Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Alexander Stewart*, Emma Sinclair, Joseph Chi Fung Ng, Joselli Silva O’Hare, Audrey Page, Ilaria Serangeli, Christian Margreitter, Federica Orsenigo, Katherine Longman, Cecile Frampas, Catia Costa, Holly May Lewis, Nora Kasar, Bryan Wu, David Kipling, Peter J.M. Openshaw, Christopher Chiu, J. Kenneth Baillie, Janet T. Scott, Malcolm G. SempleMelanie J. Bailey, Franca Fraternali, Deborah K. Dunn-Walters

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number807104
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 3 May 2022

Keywords

  • B cell
  • class-switch recombination (CSR)
  • COVID-19
  • ebola
  • immunity
  • repertoire
  • RSV (respiratory syncytial virus)

Fingerprint

Dive into the research topics of 'Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus'. Together they form a unique fingerprint.

Cite this