An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models
- Author
- Bert Schepens (UGent) , Loes van Schie (UGent) , Wim Nerinckx (UGent) , Kenny Roose (UGent) , Wander Van Breedam (UGent) , Daria Fijalkowska (UGent) , Simon Devos (UGent) , Wannes Weyts (UGent) , Sieglinde De Cae (UGent) , Sandrine Vanmarcke (UGent) , Chiara Lonigro, Hannah Eeckhaut (UGent) , Dries Van Herpe (UGent) , Jimmy Borloo, Ana Filipa Oliveira, João Paulo Portela Catani, Sarah Creytens (UGent) , Dorien De Vlieger, Gitte Michielsen (UGent) , Jackeline Cecilia Zavala Marchan (UGent) , George Moschonas, Iebe Rossey (UGent) , Koen Sedeyn (UGent) , Annelies Van Hecke (UGent) , Xin Zhang, Lana Langendries, Sofie Jacobs, Sebastiaan ter Horst, Laura Seldeslachts, Laurens Liesenborghs, Robbert Boudewijns, Hendrik Jan Thibaut, Kai Dallmeier, Greetje Vande Velde, Birgit Weynand, Julius Beer, Daniel Schnepf, Annette Ohnemus, Isabel Remory, Caroline S. Foo, Rana Abdelnabi, Piet Maes, Suzanne J. F. Kaptein, Joana Rocha-Pereira, Dirk Jochmans, Leen Delang, Frank Peelman (UGent) , Peter Staeheli, Martin Schwemmle, Nick Devoogdt, Dominique Tersago, Massimiliano Germani, James Heads, Alistair Henry, Andrew Popplewell, Mark Ellis, Kevin Brady, Alison Turner, Bruno Dombrecht, Catelijne Stortelers, Johan Neyts, Nico Callewaert (UGent) and Xavier Saelens (UGent)
- Organization
- 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.
- Keywords
- General Medicine, RECEPTOR-BINDING DOMAIN, TRANSFORMATION, SITES, SPIKE, ACE2
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8725327
- MLA
- Schepens, Bert, et al. “An Affinity-Enhanced, Broadly Neutralizing Heavy Chain-Only Antibody Protects against SARS-CoV-2 Infection in Animal Models.” SCIENCE TRANSLATIONAL MEDICINE, vol. 13, no. 621, 2021, doi:10.1126/scitranslmed.abi7826.
- APA
- Schepens, B., van Schie, L., Nerinckx, W., Roose, K., Van Breedam, W., Fijalkowska, D., … Saelens, X. (2021). An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models. SCIENCE TRANSLATIONAL MEDICINE, 13(621). https://doi.org/10.1126/scitranslmed.abi7826
- Chicago author-date
- Schepens, Bert, Loes van Schie, Wim Nerinckx, Kenny Roose, Wander Van Breedam, Daria Fijalkowska, Simon Devos, et al. 2021. “An Affinity-Enhanced, Broadly Neutralizing Heavy Chain-Only Antibody Protects against SARS-CoV-2 Infection in Animal Models.” SCIENCE TRANSLATIONAL MEDICINE 13 (621). https://doi.org/10.1126/scitranslmed.abi7826.
- Chicago author-date (all authors)
- Schepens, Bert, Loes van Schie, Wim Nerinckx, Kenny Roose, Wander Van Breedam, Daria Fijalkowska, Simon Devos, Wannes Weyts, Sieglinde De Cae, Sandrine Vanmarcke, Chiara Lonigro, Hannah Eeckhaut, Dries Van Herpe, Jimmy Borloo, Ana Filipa Oliveira, João Paulo Portela Catani, Sarah Creytens, Dorien De Vlieger, Gitte Michielsen, Jackeline Cecilia Zavala Marchan, George Moschonas, Iebe Rossey, Koen Sedeyn, Annelies Van Hecke, Xin Zhang, Lana Langendries, Sofie Jacobs, Sebastiaan ter Horst, Laura Seldeslachts, Laurens Liesenborghs, Robbert Boudewijns, Hendrik Jan Thibaut, Kai Dallmeier, Greetje Vande Velde, Birgit Weynand, Julius Beer, Daniel Schnepf, Annette Ohnemus, Isabel Remory, Caroline S. Foo, Rana Abdelnabi, Piet Maes, Suzanne J. F. Kaptein, Joana Rocha-Pereira, Dirk Jochmans, Leen Delang, Frank Peelman, Peter Staeheli, Martin Schwemmle, Nick Devoogdt, Dominique Tersago, Massimiliano Germani, James Heads, Alistair Henry, Andrew Popplewell, Mark Ellis, Kevin Brady, Alison Turner, Bruno Dombrecht, Catelijne Stortelers, Johan Neyts, Nico Callewaert, and Xavier Saelens. 2021. “An Affinity-Enhanced, Broadly Neutralizing Heavy Chain-Only Antibody Protects against SARS-CoV-2 Infection in Animal Models.” SCIENCE TRANSLATIONAL MEDICINE 13 (621). doi:10.1126/scitranslmed.abi7826.
- Vancouver
- 1.Schepens B, van Schie L, Nerinckx W, Roose K, Van Breedam W, Fijalkowska D, et al. An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models. SCIENCE TRANSLATIONAL MEDICINE. 2021;13(621).
- IEEE
- [1]B. Schepens et al., “An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models,” SCIENCE TRANSLATIONAL MEDICINE, vol. 13, no. 621, 2021.
@article{8725327,
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.}},
articleno = {{eabi7826}},
author = {{Schepens, Bert and van Schie, Loes and Nerinckx, Wim and Roose, Kenny and Van Breedam, Wander and Fijalkowska, Daria and Devos, Simon and Weyts, Wannes and De Cae, Sieglinde and Vanmarcke, Sandrine and Lonigro, Chiara and Eeckhaut, Hannah and Van Herpe, Dries and Borloo, Jimmy and Oliveira, Ana Filipa and Portela Catani, João Paulo and Creytens, Sarah and De Vlieger, Dorien and Michielsen, Gitte and Zavala Marchan, Jackeline Cecilia and Moschonas, George and Rossey, Iebe and Sedeyn, Koen and Van Hecke, Annelies and Zhang, Xin and Langendries, Lana and Jacobs, Sofie and ter Horst, Sebastiaan and Seldeslachts, Laura and Liesenborghs, Laurens and Boudewijns, Robbert and Thibaut, Hendrik Jan and Dallmeier, Kai and Vande Velde, Greetje and Weynand, Birgit and Beer, Julius and Schnepf, Daniel and Ohnemus, Annette and Remory, Isabel and Foo, Caroline S. and Abdelnabi, Rana and Maes, Piet and Kaptein, Suzanne J. F. and Rocha-Pereira, Joana and Jochmans, Dirk and Delang, Leen and Peelman, Frank and Staeheli, Peter and Schwemmle, Martin and Devoogdt, Nick and Tersago, Dominique and Germani, Massimiliano and Heads, James and Henry, Alistair and Popplewell, Andrew and Ellis, Mark and Brady, Kevin and Turner, Alison and Dombrecht, Bruno and Stortelers, Catelijne and Neyts, Johan and Callewaert, Nico and Saelens, Xavier}},
issn = {{1946-6234}},
journal = {{SCIENCE TRANSLATIONAL MEDICINE}},
keywords = {{General Medicine,RECEPTOR-BINDING DOMAIN,TRANSFORMATION,SITES,SPIKE,ACE2}},
language = {{eng}},
number = {{621}},
pages = {{18}},
title = {{An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models}},
url = {{http://doi.org/10.1126/scitranslmed.abi7826}},
volume = {{13}},
year = {{2021}},
}
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