Attempted passive prophylaxis with a monoclonal anti-Burkholderia pseudomallei exopolysaccharide antibody in a murine model of melioidosis.
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.
Bottex
Chantal
C
Centre de Recherches du Service de Santé des Armées Emile Pardé, Unité de Microbiologie, La Tronche, France. cha_botte@yahoo.fr
Gauthier
Yves P
YP
Hagen
Ralf M
RM
Finke
Ernst J
EJ
Splettstösser
Wolf D
WD
Thibault
François M
FM
Neubauer
Heinrich
H
Vidal
Dominique R
DR
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D016957:Burkholderia pseudomallei / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D004195:Disease Models, Animal; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008554:Melioidosis / Q000097:blood / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma