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

By Alexander Stewart, Emma Sinclair, Joseph CF Ng, Franca Fraternali, Joselli Silvia-O'Hare, Audrey Page, Ilaria Serangeli, Christian Margreitter, Nora Kasar, Katherine Longman, Cecile Frampas, Holly-May Lewis, Catia Costa, Bryan Wu, David Kipling, Peter Openshaw, Christopher Chiu, J Kenneth Baillie, Janet Scott, Malcolm G. Semple, Melanie Bailey, Deborah Dunn-Walters

Posted 19 Aug 2021
bioRxiv DOI: 10.1101/2021.08.19.456951

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 EBOV and COVID-19 infection cohorts. We also show unique characteristics absent in RSV infection 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 risks off-target effects.

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