TY - JOUR
T1 - Pandemic, Epidemic, Endemic
T2 - B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus
AU - Stewart, Alexander
AU - Sinclair, Emma
AU - Ng, Joseph Chi Fung
AU - O’Hare, Joselli Silva
AU - Page, Audrey
AU - Serangeli, Ilaria
AU - Margreitter, Christian
AU - Orsenigo, Federica
AU - Longman, Katherine
AU - Frampas, Cecile
AU - Costa, Catia
AU - Lewis, Holly May
AU - Kasar, Nora
AU - Wu, Bryan
AU - Kipling, David
AU - Openshaw, Peter J.M.
AU - Chiu, Christopher
AU - Baillie, J. Kenneth
AU - Scott, Janet T.
AU - Semple, Malcolm G.
AU - Bailey, Melanie J.
AU - Fraternali, Franca
AU - Dunn-Walters, Deborah K.
N1 - Funding Information:
This work was funded by the MRC (MR/L01257X/1 and MC_PC_15068), BBSRC (BB/T002212/1 and BB/V011456/1), EPSRC (EP/R031118/1) and UK National Core Studies (NCSi4P programme) funding. The study “Convalescent plasma for early Ebola virus disease in Sierra Leone” (ISRCTN13990511 and PACTR201602001355272) was supported by the Wellcome Trust (Award 106491) and Bill and Melinda Gates Foundation; Public Health England Ebola Emergency Response; and the Blood Safety Programme, National Health Service Blood and Transplant. MGS was supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections. J.T.S. is supported by the Wellcome Trust (204820/Z/16/Z). M.G.S. is supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections. JTS and MGS were awarded a grant from the Enhancing Research Activity in Epidemic Situations (ERAES) program funded by the Wellcome Trust to support further research into the sequelae of Ebola virus disease. We acknowledge the support of the Medical Research Council (G0902266), the Wellcome Trust (087805/Z/08/Z), and Medical Research Council (MRC) EMINENT Network (MR/R502121/1) which is co-funded by GSK. PO is supported by a Senior Investigator award from the National Institute for Health Research (NIHR201385) and RSV Consortium in Europe (RESCEU) Horizon 2020 Framework Grant 116019. PO and CC are supported by the Biomedical Research Centre award to Imperial College Healthcare NHS Trust, Imperial’s Health Protection Research Unit in Respiratory Infections (NIHR HPRU RI), the Comprehensive Local Research Networks (CLRNs), and the MRC HIC-Vac network (MR/R005982/1). Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre and the NIHR Imperial Clinical Research Facility. The funders had no role in the collection and analysis of the samples, in the interpretation of data, in writing the report, nor in the decision to submit the paper for publication.
Publisher Copyright:
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.
PY - 2022/5/3
Y1 - 2022/5/3
N2 - 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.
AB - 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.
KW - B cell
KW - class-switch recombination (CSR)
KW - COVID-19
KW - ebola
KW - immunity
KW - repertoire
KW - RSV (respiratory syncytial virus)
UR - http://www.scopus.com/inward/record.url?scp=85130378617&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.807104
DO - 10.3389/fimmu.2022.807104
M3 - Article
C2 - 35592326
AN - SCOPUS:85130378617
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 807104
ER -