Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies
Copyright: © 2024 Wirchnianski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
PLoS pathogens - 20(2024), 4 vom: 29. Apr., Seite e1012134 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wirchnianski, Ariel S [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Bispecific |
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| Anmerkungen: |
Date Completed 23.04.2024 Date Revised 26.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.ppat.1012134 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370930819 |
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| 100 | 1 | |a Wirchnianski, Ariel S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies |
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| 500 | |a Date Revised 26.04.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2024 Wirchnianski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Bispecific |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 700 | 1 | |a Nyakatura, Elisabeth K |e verfasserin |4 aut | |
| 700 | 1 | |a Herbert, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Kuehne, Ana I |e verfasserin |4 aut | |
| 700 | 1 | |a Abbasi, Shawn A |e verfasserin |4 aut | |
| 700 | 1 | |a Florez, Catalina |e verfasserin |4 aut | |
| 700 | 1 | |a Storm, Nadia |e verfasserin |4 aut | |
| 700 | 1 | |a McKay, Lindsay G A |e verfasserin |4 aut | |
| 700 | 1 | |a Dailey, Leandrew |e verfasserin |4 aut | |
| 700 | 1 | |a Kuang, Erin |e verfasserin |4 aut | |
| 700 | 1 | |a Abelson, Dafna M |e verfasserin |4 aut | |
| 700 | 1 | |a Wec, Anna Z |e verfasserin |4 aut | |
| 700 | 1 | |a Chakraborti, Srinjoy |e verfasserin |4 aut | |
| 700 | 1 | |a Holtsberg, Frederick W |e verfasserin |4 aut | |
| 700 | 1 | |a Shulenin, Sergey |e verfasserin |4 aut | |
| 700 | 1 | |a Bornholdt, Zachary A |e verfasserin |4 aut | |
| 700 | 1 | |a Aman, M Javad |e verfasserin |4 aut | |
| 700 | 1 | |a Honko, Anna N |e verfasserin |4 aut | |
| 700 | 1 | |a Griffiths, Anthony |e verfasserin |4 aut | |
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| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jonathan R |e verfasserin |4 aut | |
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