@article{5529d29ae9c3442a8447aac6d0e69cae,
title = "Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection",
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.",
keywords = "B cell repertoire, Ebola, IgG subclass, antibody evolution, public clonotype",
author = "Davis, {Carl W.} and Jackson, {Katherine J.L.} and McElroy, {Anita K.} and Peter Halfmann and Jessica Huang and Chakravarthy Chennareddy and Piper, {Ashley E.} and Yvonne Leung and Albari{\~n}o, {C{\'e}sar G.} and Ian Crozier and Ellebedy, {Ali H.} and John Sidney and Alessandro Sette and Tianwei Yu and Nielsen, {Sandra C.A.} and Goff, {Arthur J.} and Spiropoulou, {Christina F.} and Saphire, {Erica Ollman} and Guy Cavet and Yoshihiro Kawaoka and Mehta, {Aneesh K.} and Glass, {Pamela J.} and Boyd, {Scott D.} and Rafi Ahmed",
note = "Funding Information: We thank the nurses and physicians of the Emory Serious Communicable Diseases Program for their assistance in collecting samples; Aaron Rae of the Children{\textquoteright}s Healthcare of Atlanta and Emory University Pediatric Flow Cytometry Core for performing cell sorting; David DiLillo of the Rockefeller University for providing mAbs c13C6 and 1H3 containing human IgG1 Fc regions; Marnie Fusco for scientific discussions; and Joshua Shamblin, Susanne Wollen, Adrienne Kimmel, Joshua Moore, and Jimmy Fiallos for assistance with in vivo studies. These studies were funded by DARPA ( W31P4Q-14-1-0010 ). Funding for A.K. McElroy was from Burroughs Wellcome CAMS ( 1013362.01 ) and NIH ( K08 AI119448 ). Funding for A.S. was from NIH ( HHSN272201400045C and P01 AI106695 ). Support for G.C. and Y.L. was from the Bill and Melinda Gates Foundation . Funding for E.S. was from NIH ( U19 AI109762 ). Support for Y.K. was from the Research Program on Emerging and Re-emerging Infectious Diseases from AMED ( JP19fk0108029h0002 and JP19fm0208101j0001 ). Funding Information: We thank the nurses and physicians of the Emory Serious Communicable Diseases Program for their assistance in collecting samples; Aaron Rae of the Children's Healthcare of Atlanta and Emory University Pediatric Flow Cytometry Core for performing cell sorting; David DiLillo of the Rockefeller University for providing mAbs c13C6 and 1H3 containing human IgG1 Fc regions; Marnie Fusco for scientific discussions; and Joshua Shamblin, Susanne Wollen, Adrienne Kimmel, Joshua Moore, and Jimmy Fiallos for assistance with in vivo studies. These studies were funded by DARPA (W31P4Q-14-1-0010). Funding for A.K. McElroy was from Burroughs Wellcome CAMS (1013362.01) and NIH (K08 AI119448). Funding for A.S. was from NIH (HHSN272201400045C and P01 AI106695). Support for G.C. and Y.L. was from the Bill and Melinda Gates Foundation. Funding for E.S. was from NIH (U19 AI109762). Support for Y.K. was from the Research Program on Emerging and Re-emerging Infectious Diseases from AMED (JP19fk0108029h0002 and JP19fm0208101j0001). C.W.D. K.J.L.J. A.J.G. P.H. I.C. P.J.G. G.C. Y.K. C.F.S. S.D.B. and R.A. designed and analyzed experiments. A.K. McElroy, A.K. Mehta, and R.A. designed the clinical study. A.K. Mehta ran the clinical study. C.W.D. K.J.L.J. A.K. McElroy, P.H. J.H. C.C. A.E.P. Y.L. C.G.A. and A.H.E. performed experiments. J.S. A.S. A.H.E. G.C. and E.O.S. provided novel reagents and methods and gave experimental suggestions. C.W.D. K.J.L.J. S.D.B. and R.A. wrote the paper. R.A. is the inventor on a patent filed by Emory University relating to the antibodies described in this work. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = may,
day = "30",
doi = "10.1016/j.cell.2019.04.036",
language = "English",
volume = "177",
pages = "1566--1582.e17",
journal = "Cell",
issn = "0092-8674",
number = "6",
}