Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses.
Immunology
Structural biology
Virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 Apr 2023
21 Apr 2023
Historique:
received:
17
11
2022
revised:
07
02
2023
accepted:
24
03
2023
medline:
18
4
2023
entrez:
17
4
2023
pubmed:
18
4
2023
Statut:
ppublish
Résumé
SARS-CoV-2 variants evade current monoclonal antibody therapies. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies taking advantage of the avidity and synergy provided by targeting different epitopes. Here we used controlled Fab-arm exchange to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader antibodies that also neutralize SARS-CoV. We demonstrated that the parental antibodies rely on avidity for neutralization using bsAbs containing one irrelevant Fab arm. Using mass photometry to measure the formation of antibody:spike complexes, we determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike, observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent agents to combat circulating and future SARS-like coronaviruses.
Identifiants
pubmed: 37063468
doi: 10.1016/j.isci.2023.106540
pii: S2589-0042(23)00617-X
pmc: PMC10065043
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106540Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 COVA MAbs. There are no other competing interests.
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