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.
journal_name
Celljournal_title
Cellauthors
Davis CW,Jackson KJL,McElroy AK,Halfmann P,Huang J,Chennareddy C,Piper AE,Leung Y,Albariño CG,Crozier I,Ellebedy AH,Sidney J,Sette A,Yu T,Nielsen SCA,Goff AJ,Spiropoulou CF,Saphire EO,Cavet G,Kawaoka Y,Mehta AK,doi
10.1016/j.cell.2019.04.036subject
Has Abstractpub_date
2019-05-30 00:00:00pages
1566-1582.e17issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(19)30455-6journal_volume
177pub_type
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