Monoclonal antibodies protect against pandrug-resistant Klebsiella pneumoniae

Abstract

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 oncology¹ and autoimmunity², are rarely used for infectious diseases and not yet used for antimicrobial resistance³. 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.