Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.
Unology
immune response
virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Dec 2022
22 Dec 2022
Historique:
received:
31
05
2022
revised:
07
10
2022
accepted:
10
11
2022
pubmed:
22
11
2022
medline:
22
11
2022
entrez:
21
11
2022
Statut:
ppublish
Résumé
The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.
Identifiants
pubmed: 36406861
doi: 10.1016/j.isci.2022.105596
pii: S2589-0042(22)01868-5
pmc: PMC9664764
doi:
Types de publication
Journal Article
Langues
eng
Pagination
105596Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
M.T., K.S., H.S., T.T., Y.T., S.M., H.F., M.S., T.M., K.K., Y.I., H.I., M.N., Y.Kitagawa, and Y.Kawaoka declared that they are co-inventors on a patent application on neutralizing antibodies described in this article (PCT/JP2021/35159). The remaining authors have no declarations of interest.
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