Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection
Open accessAbstract
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.
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Non-neutralizing binding antibodies have shown protective effects in many viral infections.
“Binding, non-neutralizing antibodies have also been shown to have a protective effect in many viral infections (Asthagiri Arunkumar et al., 2019; DiLillo et al., 2014; Saphire et al., 2018)”
From SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2 (2021) · cites this paper as Saphire et al., 2018
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Amanat, F., Thapa, M., Lei, T., Ahmed, S. M. S., Adelsberg, D. C., Carreño, J. M., Strohmeier, S., Schmitz, A. J., Zafar, S., Zhou, J. Q., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.005 · Cited by 273 · see citing works
Self-citationWidjaja, I., Wang, C., van Haperen, R., Gutiérrez-Álvarez, J., van Dieren, B., Okba, N. M. A., Raj, V. S., Li, W., Fernandez-Delgado, R., Grosveld, F., et al. (2019) · Emerging Microbes & Infections · doi:10.1080/22221751.2019.1597644 · Cited by 115 · see citing works
Self-citation
- Authors
- Saphire, E. O., Schendel, S. L., Fusco, M. L., Gangavarapu, K., Gunn, B. M., Wec, A. Z., Halfmann, P. J., Brannan, J. M., Herbert, A. S., Qiu, X., Wagh, K., He, S., Giorgi, E. E., Theiler, J., Pommert, K. B. J., Krause, T. B., Turner, H. L., Murin, C. D., Pallesen, J., Davidson, E., Ahmed, R., Aman, M. J., Bukreyev, A., Burton, D. R., Crowe, J. E., Davis, C. W., Georgiou, G., Krammer, F., Kyratsous, C. A., Lai, J. R., Nykiforuk, C., Pauly, M. H., Rijal, P., Takada, A., Townsend, A. R., Volchkov, V., Walker, L. M., Wang, C.-I., Zeitlin, L., Doranz, B. J., Ward, A. B., Korber, B., Kobinger, G. P., Andersen, K. G., Kawaoka, Y., Alter, G., Chandran, K., & Dye, J. M.
- Affiliations
- Scripps Research Institute (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Albert Einstein College of Medicine (US)
- University of Wisconsin–Madison (US)
- United States Army Medical Research Institute of Infectious Diseases (US)
- Public Health Agency of Canada (CA)
- Los Alamos National Laboratory (US)
- Integral Molecular (United States) (US)
- Emory University (US)
- Integrated BioTherapeutics (United States) (US)
- The University of Texas Medical Branch at Galveston (US)
- Vanderbilt University Medical Center (US)
- The University of Texas at Austin (US)
- Icahn School of Medicine at Mount Sinai (US)
- Regeneron (United States) (US)
- Emergent BioSolutions (Canada) (CA)
- Mapp Biopharmaceutical (United States) (US)
- University of Oxford (GB)
- Hokkaido University (JP)
- Centre National de la Recherche Scientifique (FR)
- Adimab (United States) (US)
- Agency for Science, Technology and Research (SG)
- Université Laval (CA)
- Corresponding author
- Saphire, Erica Ollmann
- Kobinger, Gary P.
- Andersen, Kristian G.
- Kawaoka, Yoshihiro
- Alter, Galit
- Chandran, Kartik
- Dye, John M.
- ORCID
- Saphire, Erica Ollmann
- Schendel, Sharon L.
- Gangavarapu, Karthik
- Gunn, Bronwyn M.
- Wec, Anna Z.
- Halfmann, Peter J.
- Brannan, Jennifer M.
- Herbert, Andrew S.
- Qiu, Xiangguo
- Wagh, Kshitij
- He, Shihua
- Giorgi, Elena E.
- Theiler, James
- Turner, Hannah L.
- Murin, Charles D.
- Pallesen, Jesper
- Davidson, Edgar
- Ahmed, Rafi
- Aman, M. Javad
- Bukreyev, Alexander
- Burton, Dennis R.
- Crowe, James E.
- Davis, Carl W.
- Georgiou, George
- Krammer, Florian
- Kyratsous, Christos A.
- Lai, Jonathan R.
- Rijal, Pramila
- Takada, Ayato
- Townsend, Alain R.
- Volchkov, Viktor
- Walker, Laura M.
- Wang, Cheng-I.
- Zeitlin, Larry
- Doranz, Benjamin J.
- Ward, Andrew B.
- Korber, Bette
- Kobinger, Gary P.
- Andersen, Kristian G.
- Kawaoka, Yoshihiro
- Alter, Galit
- Chandran, Kartik
- Dye, John M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 174
- Issue
- 4
- Pages
- 938-952.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6102396
- OpenAlex
- W2885550272
- Cited by
- 212
- References
- 88
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 20 · 2023: 18 · 2022: 18 · 2021: 44 · 2020: 36 · 2019: 41 · 2018: 8
- FWCI
- 24.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (HHSN272201400058C, U19AI135995, IAF311007)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- Ebola virus, monoclonal antibodies, glycoproteins, secreted glycoprotein, antibody neutralization, immune effector functions, epitope mapping, glycan structure, natural killer cells, phagocytosis, mouse challenge protection, cross-reactivity, vaccine response
- MeSH terms
- Animals, Antibodies, Monoclonal, Epitopes, Female, Immunization, Membrane Glycoproteins, Mice, Inbred BALB C, Treatment Outcome, Hemorrhagic Fever, Ebola, Ebolavirus, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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