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Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2011 May; Vol. 66 (5), pp. 1100-9. Date of Electronic Publication: 2011 Feb 24. - Publication Year :
- 2011
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Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacokinetics
Disease Models, Animal
Female
Injections, Intravenous
Lung immunology
Lung microbiology
Lung pathology
Mice
Mice, Inbred C57BL
Pseudomonas aeruginosa pathogenicity
Treatment Outcome
Antibodies, Bacterial administration & dosage
Antibodies, Monoclonal administration & dosage
Immunoglobulin M administration & dosage
Immunotherapy methods
Pneumonia, Bacterial drug therapy
Pseudomonas Infections drug therapy
Pseudomonas aeruginosa immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 21393169
- Full Text :
- https://doi.org/10.1093/jac/dkr038