RT Journal Article
SR Electronic
T1 Systematic analysis of human antibody response to ebolavirus glycoprotein reveals high prevalence of neutralizing public clonotypes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.12.476089
DO 10.1101/2022.01.12.476089
A1 Elaine C. Chen
A1 Pavlo Gilchuk
A1 Seth J. Zost
A1 Philipp A. Ilinykh
A1 Elad Binshtein
A1 Kai Huang
A1 Luke Myers
A1 Stefano Bonissone
A1 Samuel Day
A1 Chandrahaas R. Kona
A1 Andrew Trivette
A1 Joseph X. Reidy
A1 Rachel E. Sutton
A1 Christopher Gainza
A1 Summer Monroig
A1 Edgar Davidson
A1 Erica Ollmann Saphire
A1 Benjamin J. Doranz
A1 Natalie Castellana
A1 Alexander Bukreyev
A1 Robert H. Carnahan
A1 James E. Crowe, Jr
YR 2022
UL http://biorxiv.org/content/early/2022/01/13/2022.01.12.476089.abstract
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.