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

• DOI: 10.3389/fimmu.2022.807104
• Publication Date: 2022-05-03T06:51:05Z
• Authors: Alexander Stewart; Emma Sinclair; Joseph Chi-Fung Ng; Joselli Silva O’Hare; Audrey Page; Ilaria Serangeli; Christian Margrei...; Federica Orsenigo; Katherine Longman; Cecile Frampas; Catia Costa; Holly-May Lewis; Nora Kasar; Bryan Wu; David Kipling; Peter JM Openshaw; Christopher Chiu; J Kenneth Baillie; Janet T. Scott; Malcolm G. Semple; Melanie J. Bailey; Franca Fraternali; Deborah K. Dunn-W...
• Keywords: MECHANISM; 0301 basic medicine; 570; ANTIBODY-RESPONSES; class-switch recombination (CSR); HYPERMUTATION; ebola; antibody sequencing; bioinformatics; Immunology; Antibodies, Viral; Antibodies; CYTIDINE DEAMINASE AID; 03 medical and health sciences; RSV (respiratory syncytial virus); 1108 Medical Microbiology; ebola; 616; INFECTION; Immunology and Allergy; Humans; Viral; Pandemics; B cell; Science & Technology; IGM; SARS-CoV-2; MEMORY; repertoire; COVID-19; RC581-607; Hemorrhagic Fever, Ebola; Ebolavirus; immunity; 3. Good health; 1107 Immunology; Respiratory Syncytial Virus, Human; Hemorrhagic Fever; Respiratory Syncytial Virus; Immunologic diseases. Allergy; Life Sciences & Biomedicine; B cell; class-switch recombination (CSR); COVID-19; ebola; immunity; repertoire; RSV (respiratory syncytial virus);; Human; CLASS SWITCH RECOMBINATION

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.