Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection
| Autor: | Bernhard Ryffel, O. Rutschi, L. Fauconnier, M. P. Rudolf, Thomas Secher, Agata Szade, S. C. Fas |
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| Rok vydání: | 2011 |
| Předmět: |
Microbiology (medical)
Lung injury pulmonary infections Mice Pneumonia Bacterial medicine Animals Pseudomonas Infections Pharmacology (medical) Lung anti-inflammatory Pharmacology Innate immune system biology business.industry anti-infective antibody Respiratory disease Antibodies Monoclonal respiratory system medicine.disease Antibodies Bacterial respiratory tract diseases Mice Inbred C57BL Disease Models Animal Pneumonia Treatment Outcome Infectious Diseases medicine.anatomical_structure Immunoglobulin M acute pneumonia Injections Intravenous Pseudomonas aeruginosa Immunology biology.protein Female Immunotherapy Antibody business Panobacumab |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 66:1100-1109 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkr038 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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