Monoclonal antibodies protect against pandrug-resistant Klebsiella pneumoniae

The ‘silent pandemic’ caused by antimicrobial resistance requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative and safe drugs in oncology 1 and autoimmunity 2 , are rarely used for infectious diseases and not yet used for antimicrobia...

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Vydáno v:	Nature (London) Ročník 646; číslo 8087; s. 1204 - 1213
Hlavní autoři:	Roscioli, Emanuele, Zucconi Galli Fonseca, Vittoria, Bosch, Soraya Soledad, Paciello, Ida, Maccari, Giuseppe, Cardinali, Giulia, Batani, Giampiero, Stazzoni, Samuele, Tiseo, Giusy, Giordano, Cesira, Yuwei, Shen, Capoccia, Laura, Cardamone, Dario, Ridelfi, Matteo, Troisi, Marco, Manganaro, Noemi, Mugnaini, Chiara, De Santi, Concetta, Ciabattini, Annalisa, Cerofolini, Linda, Fragai, Marco, Licastro, Danilo, Wyres, Kelly, Dortet, Laurent, Barnini, Simona, Nicolau, David P., Menichetti, Francesco, Falcone, Marco, Abdelraouf, Kamilia, Sala, Claudia, Kabanova, Anna, Rappuoli, Rino
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 30.10.2025 Nature Publishing Group
Témata:	14/1 631/250/2499 631/250/255/1318 631/326/421 Animals Anti-Bacterial Agents - pharmacology Antibiotics Antibodies Antibodies, Monoclonal - immunology Antibodies, Monoclonal - isolation & purification Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Antigens Antimicrobial resistance Bacteremia - microbiology Bacteremia - prevention & control Bacteria Bacterial Capsules - immunology Bactericidal activity Carbapenems Drug resistance Drug Resistance, Bacterial - drug effects Drug Resistance, Multiple, Bacterial - drug effects Drug Resistance, Multiple, Bacterial - immunology FDA approval Female Flow cytometry Genomes Humanities and Social Sciences Humans Infectious diseases Klebsiella Klebsiella Infections - drug therapy Klebsiella Infections - immunology Klebsiella Infections - microbiology Klebsiella Infections - prevention & control Klebsiella pneumoniae Klebsiella pneumoniae - classification Klebsiella pneumoniae - drug effects Klebsiella pneumoniae - genetics Klebsiella pneumoniae - growth & development Klebsiella pneumoniae - immunology Klebsiella pneumoniae - pathogenicity Macrophages Macrophages - immunology Macrophages - microbiology Male Medical innovations Mice Monoclonal antibodies multidisciplinary Nosocomial infections O Antigens - immunology Pathogens Science Science (multidisciplinary) Septicemia Virulence
ISSN:	0028-0836, 1476-4687, 1476-4687
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Shrnutí:	The ‘silent pandemic’ caused by antimicrobial resistance requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative and safe drugs in oncology 1 and autoimmunity 2 , are rarely used for infectious diseases and not yet used for antimicrobial resistance 3 . Here we applied an antigen-agnostic strategy to isolate extremely potent human mAbs against Klebsiella pneumoniae sequence type 147 (ST147), a hypervirulent and pandrug-resistant lineage that is spreading globally. Isolated mAbs target the KL64 capsule and the O-antigen. However, although mAbs displayed bactericidal activity in the picomolar range in vitro, only the capsule-specific mAbs were protective against fulminant bloodstream infection by ST147 and two geographically and genetically distant carbapenem-resistant KL64-bearing K. pneumoniae . Protection observed in vivo correlated with in vitro bacterial uptake by macrophages and enchained bacterial growth. Our study thus describes a mAb that protects against pandrug-resistant K. pneumoniae and provides a strategy to isolate mAbs and identify mAbs that confer protection against bacteria with antimicrobial resistance. Capsule-specific human monoclonal antibodies are protective against bloodstream infection by Klebsiella pneumoniae sequence type 147 in a mouse model of septicaemia, and could provide a useful strategy against pathogens with antimicrobial resistance.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-025-09391-3