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

• Type of Material: Article
• Authors: Carl Davis, Emory University; Katherine JL Jackson, Stanford University; Anita McElroy, Emory University; Peter Halfmann, University of Wisconsin; Jessica Huang, Emory University; Chakravarthy Chennareddy, Emory University; Ashley E Piper, US Army; Tianwei Yu, Emory University; Aneesh Mehta, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2019-05-30
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Elsevier Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2019.04.036
• Title of Journal or Parent Work: Cell
• Volume: 177
• Issue: 6
• Start Page: 1566
• End Page: +
• Grant/Funding Information: Funding for E.S. was from NIH (U19 AI109762).; These studies were funded by DARPA (W31P4Q-14-1-0010).; Funding for A.S. was from NIH (HHSN272201400045C and P01 AI106695).; Support for Y.K. was from the Research Program on Emerging and Re-emerging Infectious Diseases from AMED (JP19fk0108029h0002 and JP19fm0208101j0001).; Support for G.C. and Y.L. was from the Bill and Melinda Gates Foundation.; Funding for A.K. McElroy was from Burroughs Wellcome CAMS (1013362.01) and NIH (K08 AI119448).
• Keywords: Science & Technology; HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; SEQUENCE; GLYCOPROTEIN; GENERATION; PROTECTION; Cell Biology; DISEASE; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; PERSISTENCE; SEMINAL FLUID; IGG SUBCLASS DISTRIBUTION
• Research Categories: Biology, Virology; Health Sciences, Pathology; Health Sciences, Immunology

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.