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Attempted Passive Prophylaxis with a Monoclonal Anti-Burkholderia Pseudomallei Exopolysaccharide Antibody in a Murine Model of Melioidosis
Authors:Chantal Bottex  Yves P Gauthier  Ralf M Hagen  Ernst J Finke  Wolf D Splettstösser  François M Thibault
Institution:1. Centre de Recherches du Service de Santé des Armées Emile Pardé, Unité de Microbiologie, La Tronche cedex, France;2. Institut für Mikrobiologie der Bundeswehr, Munich, Germany
Abstract:Melioidosis is a severe gram-negative infection caused by the facultative intracellular bacterium Burkholderia pseudomallei, which is responsible for a broad spectrum of symptoms in both humans and animals. No licensed vaccine currently exists. This study evaluated the protective effect of a monoclonal antibody (Mab Ps6F6) specific to B. pseudomallei exopolysaccharide in an outbred murine model of sub-acute melioidosis. When administered before the infectious challenge, Ps6F6 significantly increased resistance to infection and restrained bacterial burden in the spleen over a 30-days period. Patterns of IFN-γ production were similar in the treated and non treated groups of mice. However, Ps6F6 lowered IFN-γ levels over the duration of the assay period, except on day 1, suggesting a transient and rapid production of IFN-γ under Ps6F6 control. Minor but persisting increases occurred in IL-12 levels while TNF-α was detected only in the controls at the later stages of infection. No IL-10 secretion was detected in both groups of mice. These data suggest that passive prophylaxis with Mab Ps6F6 provide a moderate and transient induction of inflammatory responses in infected mice but failed to trigger a sterilizing protective immunity.
Keywords:Burkholderia pseudomallei  melioidosis  monoclonal antibody  prophylaxis  immunomodulation
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