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 Kawaoka; Aneesh K Mehta; Pamela J Glass; Scott D Boyd; Rafi Ahmed

doi:10.1016/j.cell.2019.04.036

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

Cell. 2019 May 30;177(6):1566-1582.e17. doi: 10.1016/j.cell.2019.04.036. Epub 2019 May 16.

Authors

Carl W Davis¹, Katherine J L Jackson², Anita K McElroy³, Peter Halfmann⁴, Jessica Huang¹, Chakravarthy Chennareddy¹, Ashley E Piper⁵, Yvonne Leung⁶, César G Albariño⁷, Ian Crozier⁸, Ali H Ellebedy⁹, John Sidney¹⁰, Alessandro Sette¹¹, Tianwei Yu¹², Sandra C A Nielsen¹³, Arthur J Goff⁵, Christina F Spiropoulou⁷, Erica Ollman Saphire¹⁴, Guy Cavet⁶, Yoshihiro Kawaoka¹⁵, Aneesh K Mehta¹⁶, Pamela J Glass⁵, Scott D Boyd¹³, Rafi Ahmed¹⁷

Affiliations

¹ Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
² Department of Pathology, Stanford University, Stanford, CA, USA; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
³ 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.
⁴ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
⁵ Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD, USA.
⁶ Atreca, Redwood City, CA, USA.
⁷ Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁸ 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.
⁹ 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.
¹⁰ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
¹¹ 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.
¹² Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
¹³ Department of Pathology, Stanford University, Stanford, CA, USA.
¹⁴ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA; La Jolla Institute for Immunology, La Jolla, CA, USA.
¹⁵ 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.
¹⁶ Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA.
¹⁷ Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. Electronic address: rahmed@emory.edu.

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.

Keywords: B cell repertoire; Ebola; IgG subclass; antibody evolution; public clonotype.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Amino Acid Sequence / genetics
Animals
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / isolation & purification
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
B-Lymphocytes / metabolism
B-Lymphocytes / physiology*
Chlorocebus aethiops
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
Immunoglobulin G / immunology
Jurkat Cells
Longitudinal Studies
Male
Mice
Mice, Inbred BALB C
Survivors
Vero Cells
Viral Envelope Proteins / genetics

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Ebola Vaccines
Epitopes
Glycoproteins
Immunoglobulin G
Viral Envelope Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding