PT - JOURNAL ARTICLE AU - Elaine C. Chen AU - Pavlo Gilchuk AU - Seth J. Zost AU - Philipp A. Ilinykh AU - Elad Binshtein AU - Kai Huang AU - Luke Myers AU - Stefano Bonissone AU - Samuel Day AU - Chandrahaas R. Kona AU - Andrew Trivette AU - Joseph X. Reidy AU - Rachel E. Sutton AU - Christopher Gainza AU - Summer Monroig AU - Edgar Davidson AU - Erica Ollmann Saphire AU - Benjamin J. Doranz AU - Natalie Castellana AU - Alexander Bukreyev AU - Robert H. Carnahan AU - James E. Crowe, Jr TI - Systematic analysis of human antibody response to ebolavirus glycoprotein reveals high prevalence of neutralizing public clonotypes AID - 10.1101/2022.01.12.476089 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.01.12.476089 4099 - http://biorxiv.org/content/early/2022/01/13/2022.01.12.476089.short 4100 - http://biorxiv.org/content/early/2022/01/13/2022.01.12.476089.full AB - Understanding the human antibody response to emerging viral pathogens is key to epidemic preparedness. As the size of the B cell response to a pathogenic virus protective antigen is undefined, we performed deep paired heavy and light chain sequencing in EBOV-GP specific memory B cells, allowing analysis of the ebolavirus-specific antibody repertoire both genetically and functionally. This approach facilitated investigation of the molecular and genetic basis for evolution of cross-reactive antibodies by elucidating germline-encoded properties of antibodies to EBOV and identification of the overlap between antibodies in the memory B-cell and serum repertoire. We identified 73 public clonotypes to EBOV, 20% of which encoded antibodies with neutralization activity and capacity to protect in vivo. This comprehensive analysis of the public and private antibody repertoire provides insight into the molecular basis of the humoral immune response to EBOV-GP, which informs vaccine design of new vaccines and improved therapeutics.Competing Interest StatementE.D. and B.J.D. are employees of Integral Molecular, and B.J.D.is a shareholder in that company. J.E.C. has served as a consultant for Eli Lilly, GlaxoSmithKline and Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. All other authors declare no competing interests.