Systematic analysis of human antibody response to ebolavirus glycoprotein shows high prevalence of neutralizing public clonotypes

Elaine C. Chen, Pavlo Gilchuk, Seth J. Zost, Philipp A. Ilinykh, Elad Binshtein, Kai Huang, Luke Myers, Stefano Bonissone, Samuel Day, Chandrahaas R. Kona, Andrew Trivette, Joseph X. Reidy, Rachel E. Sutton, Christopher Gainza, Summer Diaz, Jazmean K. Williams, Christopher N. Selverian, Edgar Davidson, Erica Ollmann Saphire, Benjamin J. DoranzNatalie Castellana, Alexander Bukreyev, Robert H. Carnahan, James E. Crowe

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 poorly defined, we perform deep paired heavy- and light-chain sequencing in Ebola virus glycoprotein (EBOV-GP)-specific memory B cells, allowing analysis of the ebolavirus-specific antibody repertoire both genetically and functionally. This approach facilitates investigation of the molecular and genetic basis for the 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 identify 73 public clonotypes of EBOV, 20% of which encode antibodies with neutralization activity and capacity to protect mice 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 the design of vaccines and improved therapeutics.

Original languageEnglish (US)
Article number112370
JournalCell Reports
Volume42
Issue number4
DOIs
StatePublished - Apr 25 2023
Externally publishedYes

Keywords

  • CP: Immunology
  • Ebola
  • adaptive immunity
  • antibodies
  • human
  • monoclonal
  • repertoire

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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