IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
Animals
Antibodies, Bispecific
/ genetics
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
/ therapeutic use
COVID-19
Cricetinae
Humans
Immunoglobulin G
/ genetics
Mice
Neutralization Tests
SARS-CoV-2
/ genetics
Single-Chain Antibodies
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 10 2022
03 10 2022
Historique:
received:
26
11
2021
accepted:
26
08
2022
entrez:
3
10
2022
pubmed:
4
10
2022
medline:
6
10
2022
Statut:
epublish
Résumé
Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.
Identifiants
pubmed: 36192374
doi: 10.1038/s41467-022-33030-4
pii: 10.1038/s41467-022-33030-4
pmc: PMC9528872
doi:
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Immunoglobulin G
0
Single-Chain Antibodies
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5814Subventions
Organisme : NIAID NIH HHS
ID : R01 AI161152
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142790
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA260543
Pays : United States
Informations de copyright
© 2022. The Author(s).
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