Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection.

摘要

OBJECTIVES: To investigate the in vivo efficacy in a murine pulmonary infection model of panobacumab (KBPA101), a human IgM monoclonal antibody directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11, and to describe the anti-inflammatory effects in the lung as a consequence of the treatment. METHODS: We established an experimental murine model of acute pneumonia by intranasal administration of P. aeruginosa serotype O11. Mice were treated, after infection, with a single intravenous injection of panobacumab and panobacumab lung bioavailability was assessed. Inflammatory parameters such as pro-inflammatory cytokine production and neutrophil recruitment in broncho-alveolar lavage fluid (BALF) were measured and bacterial load in the lung was analysed. RESULTS: Panobacumab plays a significant role in addition to the host innate immune response, leading to improved control of pulmonary infection. The IgM antibody is able to reach the broncho-alveolar space and reduce the pulmonary bacterial load as well as lung inflammation in a dose-dependent manner. Furthermore, panobacumab treatment leads to enhanced neutrophil recruitment in BALF while reducing the host-derived production of pro-inflammatory mediators and lung injury. CONCLUSIONS: These data provide evidence that panobacumab, an IgM-based immunotherapeutic, is highly efficacious in controlling acute lung infection by enhancing the natural innate immune response.