Premium
Engineered Multivalent Nanobodies Potently and Broadly Neutralize SARS‐CoV‐2 Variants
Author(s) -
Zupancic Jennifer M.,
Schardt John S.,
Desai Alec A.,
Makowski Emily K.,
Smith Matthew D.,
Pornnoppadol Ghasidit,
Garcia de Mattos Barbosa Mayara,
Cascalho Marilia,
Lanigan Thomas M.,
Tessier Peter M.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100099
Subject(s) - epitope , antibody , virology , neutralizing antibody , covid-19 , neutralization , chemistry , computational biology , plasma protein binding , epitope mapping , biology , microbiology and biotechnology , virus , genetics , medicine , disease , pathology , infectious disease (medical specialty)
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.