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

• Published in: Cell Vol. 177; no. 6; pp. 1566 - 1582.e17
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2019; Cell Press
• Subjects: Adult; Amino Acid Sequence - genetics; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; antibody evolution; B cell repertoire; B-Lymphocytes - metabolism; B-Lymphocytes - physiology; Chlorocebus aethiops; Ebola; Ebola Vaccines - immunology; Ebolavirus - genetics; Ebolavirus - metabolism; Ebolavirus - pathogenicity; Epitopes - blood; Female; Glycoproteins - genetics; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - metabolism; Hemorrhagic Fever, Ebola - virology; Humans; IgG subclass; Immunoglobulin G - immunology; Jurkat Cells; Longitudinal Studies; Male; Mice; Mice, Inbred BALB C; public clonotype; Survivors; Vero Cells; Viral Envelope Proteins - genetics; antibody evolution; B cell repertoire; Ebola; IgG subclass; public clonotype
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2019.04.036

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. [Display omitted] •Ebola virus infection causes massive recruitment of naive B cells•Virus-specific antibodies continue to class-switch and mutate for months after acute infection•Protective antibodies can be neutralizing or non-neutralizing and can appear early•Convergent, protective antibody rearrangements are seen in multiple donors A longitudinal study of Ebola virus infection survivors maps out the antibody features that confer protection, with potential implications for vaccination.