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

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

  2. Author Address

    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA., Department of Pathology, Stanford University, Stanford, CA, USA; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA; Division of Pediatric Infectious Disease, Emory University, Atlanta, GA, USA; Division of Pediatric Infectious Disease, University of Pittsburgh, Pittsburgh, PA, USA., Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA., Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD, USA., Atreca, Redwood City, CA, USA., Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA., Integrated Research Facility at Fort Detrick, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institutes, Frederick, MD, USA., Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA; Division of Immunobiology, Department of Pathology and Immunology Washington University School of Medicine, St. Louis, MO, USA., Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; Department of Medicine, University of California San Diego, La Jolla, CA, USA., Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA., Department of Pathology, Stanford University, Stanford, CA, USA., Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA; La Jolla Institute for Immunology, La Jolla, CA, USA., Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA; Division of Virology, Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan., Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA., Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. Electronic address: rahmed@emory.edu.,
    1. Year: 2019
    2. Date: MAY 30
    3. Epub Date: 2019 05 10
  2. Journal: Cell
    1. 177
    2. 6
    3. Pages: 1566-1582.e17
  4. Type of Article: Article
  5. ISSN: 0092-8674
  1. 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. Copyright © 2019 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2019.04.036
  3. PMID: 31104840
  4. View record in Web of Science®
  5. WOS: 000469415100020
  6. PII : S0092-8674(19)30455-6

Library Notes

  1. Fiscal Year: FY2018-2019
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