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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection
Cell, Volume 174, No. 4, Year 2018
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Description
Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses. The systematic assessment of the effector functions and binding sites of antibodies against Ebola virus provides a generalizable framework to evaluate the determinants of antibody-mediated protection in viral disease. © 2018 Elsevier Inc.
Authors & Co-Authors
Saphire, Erica Ollmann
United States, San Diego
Scripps Research Institute
Schendel, Sharon L.
United States, San Diego
Scripps Research Institute
Fusco, Marnie L.
United States, San Diego
Scripps Research Institute
Gangavarapu, Karthik
United States, San Diego
Scripps Research Institute
Gunn, Bronwyn M.
Unknown Affiliation
Halfmann, Peter J.
United States, Madison
University of Wisconsin-madison
Herbert, Andrew S.
United States, Arlington
United States Army
Qiu, Xiangguo
Canada, Ottawa
Public Health Agency of Canada
Wagh, Kshitij
United States, Los Alamos
Los Alamos National Laboratory
Giorgi, Elena Edi
United States, Los Alamos
Los Alamos National Laboratory
Turner, Hannah L.
United States, San Diego
Scripps Research Institute
Murin, Charles Daniel
United States, San Diego
Scripps Research Institute
Davidson, Edgar
United States, Philadelphia
Integral Molecular, Inc.
Ahmed, Rafi S.
United States, Atlanta
Emory University
Bukreyev, Alexander A.
United States, Galveston
The University of Texas Medical Branch at Galveston
Burton, Dennis Raymond
United States, San Diego
Scripps Research Institute
Crowe, James E.
United States, Nashville
Vanderbilt University Medical Center
Georgiou, George
United States, Austin
The University of Texas at Austin
Krammer, Florian H.
United States, New York
Icahn School of Medicine at Mount Sinai
Lai, Jonathan R.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Pauly, Michael H.
United States, San Diego
Mapp Biopharmaceutical
Rijal, Pramila
United Kingdom, Oxford
University of Oxford
Takada, Ayato
Japan, Sapporo
Hokkaido University
Townsend, Alain R.M.
United Kingdom, Oxford
University of Oxford
Volchkov, Viktor E.
France, Paris
Inserm
Walker, Laura M.
Unknown Affiliation
Zeitlin, Larry
United States, San Diego
Mapp Biopharmaceutical
Doranz, Benjamin J.
United States, Philadelphia
Integral Molecular, Inc.
Ward, Andrew B.
United States, San Diego
Scripps Research Institute
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
Kobinger, Gary P.
Canada, Quebec
Université Laval
Andersen, Kristian G.
United States, San Diego
Scripps Research Institute
Kawaoka, Yoshihiro K.
United States, Madison
University of Wisconsin-madison
Alter, Galit
Unknown Affiliation
Chandran, Kartik
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Dye, John M.
United States, Arlington
United States Army
Statistics
Citations: 137
Authors: 36
Affiliations: 20
Identifiers
Doi:
10.1016/j.cell.2018.07.033
ISSN:
00928674
Research Areas
Infectious Diseases
Study Approach
Systematic review