AUTHOR=Stewart Alexander , Sinclair Emma , Ng Joseph Chi-Fung , O’Hare Joselli Silva , Page Audrey , Serangeli Ilaria , Margreitter Christian , Orsenigo Federica , Longman Katherine , Frampas Cecile , Costa Catia , Lewis Holly-May , Kasar Nora , Wu Bryan , Kipling David , Openshaw Peter JM , Chiu Christopher , Baillie J Kenneth , Scott Janet T. , Semple Malcolm G. , Bailey Melanie J. , Fraternali Franca , Dunn-Walters Deborah K. TITLE=Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.807104 DOI=10.3389/fimmu.2022.807104 ISSN=1664-3224 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.