Attempted passive prophylaxis with a monoclonal anti-Burkholderia pseudomallei exopolysaccharide antibody in a murine model of melioidosis.

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-gamma production were similar in the treated and non treated groups of mice. However, Ps6F6 lowered IFN-gamma levels over the duration of the assay period, except on day 1, suggesting a transient and rapid production of IFN-gamma under Ps6F6 control. Minor but persisting increases occurred in IL-12 levels while TNF-alpha 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.