A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function.
Streptococcus
dual-Fab
immune function
monoclonals
therapeutics
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
08 02 2023
08 02 2023
Historique:
revised:
14
11
2022
received:
22
04
2022
accepted:
16
11
2022
pubmed:
13
12
2022
medline:
10
2
2023
entrez:
12
12
2022
Statut:
ppublish
Résumé
Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface-bound M protein. Such antibodies are typically non-opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual-Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual-Fab cis-binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single-Fab mode to the same region cannot bypass the M protein's virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti-streptococcal therapy. Our findings highlight the concept of dual-Fab cis binding as a means to access conserved, and normally non-opsonic regions, regions for protective antibody targeting.
Identifiants
pubmed: 36507602
doi: 10.15252/emmm.202216208
pmc: PMC9906385
doi:
Substances chimiques
streptococcal M protein
0
Epitopes
0
Antibodies, Monoclonal
0
Antigens, Bacterial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16208Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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