Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents.
Immunology
Virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
16 Jun 2023
16 Jun 2023
Historique:
received:
29
08
2022
revised:
10
10
2022
accepted:
22
05
2023
medline:
8
6
2023
pubmed:
8
6
2023
entrez:
8
6
2023
Statut:
ppublish
Résumé
Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing antibodies from B cells of convalescents, by using two types of receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 antibodies generated, six antibodies neutralized all strains prior to the Omicron variant, and the five antibodies were able to neutralize some of the Omicron sub-strains. Structural analysis showed that these antibodies have a variety of characteristic binding modes, such as ACE2 mimicry. We subjected a representative antibody to the hamster infection model after introduction of the N297A modification, and observed a dose-dependent reduction of the lung viral titer, even at a dose of 2 mg/kg. These results demonstrated that our antibodies have certain antiviral activity as therapeutics, and highlighted the importance of initial cell-screening strategy for the efficient development of therapeutic antibodies.
Identifiants
pubmed: 37288342
doi: 10.1016/j.isci.2023.106955
pii: S2589-0042(23)01032-5
pmc: PMC10208659
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106955Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
M.T., K.S., H.S., T.T., Y. Takahashi, S.M., H.F., M.S., T. Matsumoto, K.K., and Y. Kawaoka declare that they are co-inventors on a patent application on neutralizing antibodies described in this manuscript (PCT/JP2021/35159).
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