Engineered Multivalent Nanobodies Potently and Broadly Neutralize SARS-CoV-2 Variants.
COVID‐19
antibody
antibody fragment
camelid
polyvalency
polyvalent
protein engineering
Journal
Advanced therapeutics
ISSN: 2366-3987
Titre abrégé: Adv Ther (Weinh)
Pays: Germany
ID NLM: 101724632
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
28
04
2021
revised:
04
07
2021
entrez:
13
9
2021
pubmed:
14
9
2021
medline:
14
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34514086
doi: 10.1002/adtp.202100099
pii: ADTP202100099
pmc: PMC8420545
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2100099Subventions
Organisme : NIAID NIH HHS
ID : R01 AI048602
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI151588
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059723
Pays : United States
Informations de copyright
© 2021 Wiley‐VCH GmbH.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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