Kuzmina, Natalia A. and Younan, Patrick and Gilchuk, Pavlo and Santos, Rodrigo I. and Flyak, Andrew I. and Ilinykh, Philipp A. and Huang, Kai and Lubaki, Ndongala M. and Ramanathan, Palaniappan and Crowe, James E., Jr. and Bukreyev, Alexander (2018) Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors. Cell Reports, 24 (7). pp. 1802-1815. ISSN 2211-1247. PMCID PMC6697154. doi:10.1016/j.celrep.2018.07.035. https://resolver.caltech.edu/CaltechAUTHORS:20180829-103048502
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Abstract
Some monoclonal antibodies (mAbs) recovered from survivors of filovirus infections can protect against infection. It is currently unknown whether natural infection also induces some antibodies with the capacity for antibody-dependent enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub-neutralizing concentrations, and this effect was not restricted to mAbs with a particular epitope specificity, neutralizing capacity, or subclass. Blocking of specific Fcγ receptors reduced but did not abolish ADE that was associated with high-affinity binding antibodies, suggesting that lower-affinity interactions still cause ADE. Mutations of Fc fragments of an mAb that altered its interaction with Fc receptors rendered the antibody partially protective in vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection and facilitates dissemination of filovirus infections.
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| Additional Information: | © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 11 September 2017, Revised 12 June 2018, Accepted 10 July 2018, Available online 14 August 2018. We acknowledge the excellent technical support of Ms. Xiaoli Shen. This project received support from the U.S. NIH grant U19 AI109711 (to J.E.C. and A.B.) and Defense Threat Reduction Agency grant HDTRA1-13-1-0034 (to J.E.C. and A.B.). We are grateful to Dr. Larry Zeitlin for providing plant-derived antibody BDBV43. Author Contributions: N.A.K., P.Y., P.G., R.I.S., A.I.F., P.A.I., K.H., N.M.L., and P.R. designed and performed the experiments as well as analyzed the data. N.A.K., R.I.S., P.A.I., J.E.C., and A.B. conceived the study, designed the experiments, analyzed the data, and wrote the manuscript. All authors commented on the manuscript. Declaration of Interests: J.E.C. is a consultant for Sanofi and is on the Scientific Advisory Boards of PaxVax, CompuVax, GigaGen, and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi, and is founder of IDBiologics. P.A.I., P.G., A.B., and J.E.C. have applied for a patent that is related to this work. All other authors declared no competing interests. | |||||||||
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| Subject Keywords: | Ebola virus; filovirus; antibody; enhancement of infection; FC receptor; epitope | |||||||||
| Issue or Number: | 7 | |||||||||
| PubMed Central ID: | PMC6697154 | |||||||||
| DOI: | 10.1016/j.celrep.2018.07.035 | |||||||||
| Record Number: | CaltechAUTHORS:20180829-103048502 | |||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20180829-103048502 | |||||||||
| Official Citation: | Natalia A. Kuzmina, Patrick Younan, Pavlo Gilchuk, Rodrigo I. Santos, Andrew I. Flyak, Philipp A. Ilinykh, Kai Huang, Ndongala M. Lubaki, Palaniappan Ramanathan, James E. Crowe, Alexander Bukreyev, Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors, Cell Reports, Volume 24, Issue 7, 2018, Pages 1802-1815.e5, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2018.07.035. (http://www.sciencedirect.com/science/article/pii/S2211124718311252) | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 89274 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | Tony Diaz | |||||||||
| Deposited On: | 29 Aug 2018 17:36 | |||||||||
| Last Modified: | 16 Nov 2021 00:34 |
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