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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Published in:Nature (London) Vol. 646; no. 8087; pp. 1204 - 1213
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 30.10.2025
Nature Publishing Group
Subjects:
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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Summary: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.
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ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-025-09391-3