Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins
Abstract Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 disease. Therapeutic antibodies are being developed that interact with the viral spike proteins to limit viral infection of epithelium. We have applied a method to dramatically improve the performa...
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Nature Portfolio
2021
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oai:doaj.org-article:afac5eb9d9df4daf886de675f330ee892021-12-02T16:51:20ZImplementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins10.1038/s41598-021-89887-w2045-2322https://doaj.org/article/afac5eb9d9df4daf886de675f330ee892021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89887-whttps://doaj.org/toc/2045-2322Abstract Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 disease. Therapeutic antibodies are being developed that interact with the viral spike proteins to limit viral infection of epithelium. We have applied a method to dramatically improve the performance of anti-SARS-CoV-2 antibodies by enhancing avidity through multimerization using simple engineering to yield tetrameric antibodies. We have re-engineered six anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including three clinical trials antibodies casirivimab, imdevimab and etesevimab. The method yields tetrameric antibodies, termed quads, that retain efficient binding to the SARS-CoV-2 spike protein, show up to two orders of magnitude enhancement in neutralization of pseudovirus infection and retain potent interaction with virus variant of concern spike proteins. The tetramerization method is simple, general and its application is a powerful methodological development for SARS-CoV-2 antibodies that are currently in pre-clinical and clinical investigation.Adam LeachAmi MillerEmma BentleyGiada MattiuzzoJemima ThomasCraig McAndrewRob Van MontfortTerence RabbittsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q Adam Leach Ami Miller Emma Bentley Giada Mattiuzzo Jemima Thomas Craig McAndrew Rob Van Montfort Terence Rabbitts Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| description |
Abstract Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 disease. Therapeutic antibodies are being developed that interact with the viral spike proteins to limit viral infection of epithelium. We have applied a method to dramatically improve the performance of anti-SARS-CoV-2 antibodies by enhancing avidity through multimerization using simple engineering to yield tetrameric antibodies. We have re-engineered six anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including three clinical trials antibodies casirivimab, imdevimab and etesevimab. The method yields tetrameric antibodies, termed quads, that retain efficient binding to the SARS-CoV-2 spike protein, show up to two orders of magnitude enhancement in neutralization of pseudovirus infection and retain potent interaction with virus variant of concern spike proteins. The tetramerization method is simple, general and its application is a powerful methodological development for SARS-CoV-2 antibodies that are currently in pre-clinical and clinical investigation. |
| format |
article |
| author |
Adam Leach Ami Miller Emma Bentley Giada Mattiuzzo Jemima Thomas Craig McAndrew Rob Van Montfort Terence Rabbitts |
| author_facet |
Adam Leach Ami Miller Emma Bentley Giada Mattiuzzo Jemima Thomas Craig McAndrew Rob Van Montfort Terence Rabbitts |
| author_sort |
Adam Leach |
| title |
Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| title_short |
Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| title_full |
Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| title_fullStr |
Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| title_full_unstemmed |
Implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-SARS-CoV-2 antibodies to wildtype spike and variants of concern proteins |
| title_sort |
implementing a method for engineering multivalency to substantially enhance binding of clinical trial anti-sars-cov-2 antibodies to wildtype spike and variants of concern proteins |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/afac5eb9d9df4daf886de675f330ee89 |
| work_keys_str_mv |
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