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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.
MedLine Citation:
PMID:  21393169     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
T Secher; L Fauconnier; A Szade; O Rutschi; S C Fas; B Ryffel; M P Rudolf
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-24
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  -     ISSN:  1460-2091     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
UMR6218, CNRS, Orléans, France.
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