An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models
Abstract: Broadly neutralizing antibodies are an important treatment for individuals with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibody-based therapeutics are also essential for pandemic preparedness against future Sarbecovirus outbreaks. Camelid-derived single domain antibodies (VHHs) exhibit potent antimicrobial activity and are being developed as SARS-CoV-2–neutralizing antibody-like therapeutics. Here, we identified VHHs that neutralize both SARS-CoV-1 and SARS-CoV-2, including now circulating variants. We observed that the VHHs bound to a highly conserved epitope in the receptor binding domain of the viral spike protein that is difficult to access for human antibodies. Structure-guided molecular modeling, combined with rapid yeast-based prototyping, resulted in an affinity enhanced VHH-human immunoglobulin G1 Fc fusion molecule with subnanomolar neutralizing activity. This VHH-Fc fusion protein, produced in and purified from cultured Chinese hamster ovary cells, controlled SARS-CoV-2 replication in prophylactic and therapeutic settings in mice expressing human angiotensin converting enzyme 2 and in hamsters infected with SARS-CoV-2. These data led to affinity-enhanced selection of the VHH, XVR011, a stable anti–COVID-19 biologic that is now being evaluated in the clinic
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Science translational medicine. - 13, 621 (2021) , eabi7826, ISSN: 1946-6242
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
-
Universität
- (when)
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2021
- Creator
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Schepens, Bert
Schie, Loes van
Nerinckx, Wim
Roose, Kenny
Beer, Julius
Schnepf, Daniel
Ohnemus, Annette
Stäheli, Peter
Schwemmle, Martin
Callewaert, Nico
Saelens, Xavier
- DOI
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10.1126/scitranslmed.abi7826
- URN
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urn:nbn:de:bsz:25-freidok-2220299
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:20 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Schepens, Bert
- Schie, Loes van
- Nerinckx, Wim
- Roose, Kenny
- Beer, Julius
- Schnepf, Daniel
- Ohnemus, Annette
- Stäheli, Peter
- Schwemmle, Martin
- Callewaert, Nico
- Saelens, Xavier
- Universität
Time of origin
- 2021
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