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Engineered Multivalent Nanobodies Potently and Broadly Neutralize SARS-CoV-2 Variants

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Date 2021 Sep 13
PMID 34514086
Citations 19
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Abstract

The COVID-19 pandemic continues to be a severe threat to human health, especially due to current and emerging SARS-CoV-2 variants with potential to escape humoral immunity developed after vaccination or infection. The development of broadly neutralizing antibodies that engage evolutionarily conserved epitopes on coronavirus spike proteins represents a promising strategy to improve therapy and prophylaxis against SARS-CoV-2 and variants thereof. Herein, a facile multivalent engineering approach is employed to achieve large synergistic improvements in the neutralizing activity of a SARS-CoV-2 cross-reactive nanobody (VHH-72) initially generated against SARS-CoV. This synergy is epitope specific and is not observed for a second high-affinity nanobody against a non-conserved epitope in the receptor-binding domain. Importantly, a hexavalent VHH-72 nanobody retains binding to spike proteins from multiple highly transmissible SARS-CoV-2 variants (B.1.1.7 and B.1.351) and potently neutralizes them. Multivalent VHH-72 nanobodies also display drug-like biophysical properties, including high stability, high solubility, and low levels of non-specific binding. The unique neutralizing and biophysical properties of VHH-72 multivalent nanobodies make them attractive as therapeutics against SARS-CoV-2 variants.

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References
1.
Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi J . Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020; 9. PMC: 7723407. DOI: 10.7554/eLife.61312. View

2.
Shi R, Shan C, Duan X, Chen Z, Liu P, Song J . A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature. 2020; 584(7819):120-124. DOI: 10.1038/s41586-020-2381-y. View

3.
Van Roy M, Ververken C, Beirnaert E, Hoefman S, Kolkman J, Vierboom M . The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis. Arthritis Res Ther. 2015; 17:135. PMC: 4476083. DOI: 10.1186/s13075-015-0651-0. View

4.
Wec A, Wrapp D, Herbert A, Maurer D, Haslwanter D, Sakharkar M . Broad neutralization of SARS-related viruses by human monoclonal antibodies. Science. 2020; 369(6504):731-736. PMC: 7299279. DOI: 10.1126/science.abc7424. View

5.
Ter Meulen J, van den Brink E, Poon L, Marissen W, Leung C, Cox F . Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med. 2006; 3(7):e237. PMC: 1483912. DOI: 10.1371/journal.pmed.0030237. View