A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/126177 |
| _version_ | 1826200517024415744 |
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| author | Yu, Wen-Han Das, Jishnu Lauffenburger, Douglas A Alter, Galit |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Yu, Wen-Han Das, Jishnu Lauffenburger, Douglas A Alter, Galit |
| author_sort | Yu, Wen-Han |
| collection | MIT |
| description | The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens. While antibodies provide protection against Ebola virus, the mechanism is unclear. Gunn et al. dissect the contribution of Fc-functions to protection using a library of Ebola virus-specific antibodies. Fc function was a critical predictor of protection across neutralizing and non-neutralizing antibodies, pointing to synergy between Fc- and Fab-mediated antibody-functions against Ebola. |
| first_indexed | 2024-09-23T11:37:41Z |
| format | Article |
| id | mit-1721.1/126177 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:37:41Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1261772022-10-01T04:54:32Z A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus Yu, Wen-Han Das, Jishnu Lauffenburger, Douglas A Alter, Galit Massachusetts Institute of Technology. Department of Biological Engineering The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens. While antibodies provide protection against Ebola virus, the mechanism is unclear. Gunn et al. dissect the contribution of Fc-functions to protection using a library of Ebola virus-specific antibodies. Fc function was a critical predictor of protection across neutralizing and non-neutralizing antibodies, pointing to synergy between Fc- and Fab-mediated antibody-functions against Ebola. National Institutes of Health (U.S.) (Grant U19 AI109762) 2020-07-14T15:36:13Z 2020-07-14T15:36:13Z 2018-08 2020-03-12T14:12:50Z Article http://purl.org/eprint/type/JournalArticle 1931-3128 https://hdl.handle.net/1721.1/126177 Gunn, Bronwyn M. et al. “A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.” Cell host & microbe, vol. 24, no. 2, 2018, pp. 221-233.e5 © 2018 The Author(s) en 10.1016/J.CHOM.2018.07.009 Cell host & microbe Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Yu, Wen-Han Das, Jishnu Lauffenburger, Douglas A Alter, Galit A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title | A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title_full | A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title_fullStr | A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title_full_unstemmed | A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title_short | A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus |
| title_sort | role for fc function in therapeutic monoclonal antibody mediated protection against ebola virus |
| url | https://hdl.handle.net/1721.1/126177 |
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