The hinge-engineered IgG1-IgG3 hybrid subclass IgGh
Animals
Immunoglobulin G
/ immunology
Streptococcus pyogenes
/ immunology
SARS-CoV-2
/ immunology
Mice
Humans
Antibodies, Viral
/ immunology
COVID-19
/ immunology
Immunoglobulin Fc Fragments
/ immunology
Streptococcal Infections
/ immunology
Antibodies, Monoclonal
/ immunology
Antibodies, Bacterial
/ immunology
Phagocytosis
Female
Protein Engineering
/ methods
Mice, Inbred BALB C
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 Apr 2024
27 Apr 2024
Historique:
received:
30
06
2023
accepted:
15
04
2024
medline:
28
4
2024
pubmed:
28
4
2024
entrez:
27
4
2024
Statut:
epublish
Résumé
Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3's Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGh
Identifiants
pubmed: 38678029
doi: 10.1038/s41467-024-47928-8
pii: 10.1038/s41467-024-47928-8
doi:
Substances chimiques
Immunoglobulin G
0
Antibodies, Viral
0
Immunoglobulin Fc Fragments
0
Antibodies, Monoclonal
0
Antibodies, Bacterial
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
3600Informations de copyright
© 2024. The Author(s).
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