XAB06, a glyco-humanized broad-spectrum anti-Pseudomonas aeruginosa polyclonal antibody, protects mice in a lethal sepsis model.

The global rise of antibiotic-resistant Pseudomonas aeruginosa (PA) necessitates the development of novel therapeutic approaches. Polyclonal antibodies constitute a promising approach, as they target multiple bacterial epitopes and functions. Moreover, they have recently demonstrated renewed clinical applicability in their humanized format. We developed a glyco-humanized polyclonal antibody (GH-pAb) targeting PA by immunization of pigs with five PA serotypes frequently encountered in clinical settings. This pentavalent GH-pAb, named XAB06, exhibited binding activity against the five serotypes used for the immunization, as well as unrelated PA serotypes. No binding activity was observed against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, or Acinetobacter baumannii, demonstrating the specificity of XAB06 against PA. In addition, XAB06 showed no reactivity against human blood cells. Functional assays revealed that XAB06 significantly inhibited swarming motility, biofilm formation, and pyocyanin production, indicating interference with key virulence determinants of PA. Notably, XAB06 conferred protection in a murine model of sepsis using the reference strains PAO1, PA103, and a ST235 high-risk clone. Collectively, these findings demonstrate the broad PA coverage and the protective activity of XAB06, supporting its potential as a novel therapeutic strategy against PA.