Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection

Carl W. Davis, Katherine J.L. Jackson, Anita K. McElroy, Peter Halfmann, Jessica Huang, Chakravarthy Chennareddy, Ashley E. Piper, Yvonne Leung, César G. Albariño, Ian Crozier, Ali H. Ellebedy, John Sidney, Alessandro Sette, Tianwei Yu, Sandra C.A. Nielsen, Arthur J. Goff, Christina F. Spiropoulou, Erica Ollman Saphire, Guy Cavet, Yoshihiro KawaokaAneesh K. Mehta, Pamela J. Glass, Scott D. Boyd, Rafi Ahmed

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity. A longitudinal study of Ebola virus infection survivors maps out the antibody features that confer protection, with potential implications for vaccination.

Original languageEnglish
Pages (from-to)1566-1582.e17
JournalCell
Volume177
Issue number6
DOIs
StatePublished - May 30 2019

Keywords

  • B cell repertoire
  • Ebola
  • IgG subclass
  • antibody evolution
  • public clonotype

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