Enhanced survival during murine gram-negative bacterial sepsis by use of a murine monoclonal antibody
D. L. Dunn, W. C. Bogard Jr and F. B. Cerra
We developed a murine monoclonal antibody (5B10 MAb) that reacted in vitro
specifically to lipopolysaccharide (LPS) obtained from Escherichia coli
0111:B4. Enzyme-linked immunosorbent assay (ELISA) titers to a variety of
gram-negative bacterial whole cell and LPS antigens demonstrated that this
antibody may react with the O antigen portion of 0111:B4 LPS. We then
examined the ability of this antibody to protect mice in vivo against a
challenge of either viable bacteria or purified LPS. One milligram of 5B10
MAb was administered intraperitoneally (IP) and protected against a lethal
challenge of either viable E coli 0111:B4 or 0111:B4 LPS, but no other type
of bacterial or LPS challenge. Protection occurred in an antibody
dose-dependent manner, and as little as 0.01 mg of 5B10 MAb enhanced
survival. We concluded that IP pretreatment with a single MAb would protect
against lethal sepsis or endotoxemia in this animal model and that anti-LPS
specificity was a sufficient condition for an antibody to protect during
bacteremia, confirming the importance of LPS in the pathogenesis of
gram-negative bacterial sepsis.
