Enhanced survival during murine gram-negative bacterial sepsis by use of a murine monoclonal antibody.
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.
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000472:pathogenicity; D006090:Gram-Negative Bacteria; D007711:Klebsiella pneumoniae / Q000472:pathogenicity; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D018805:Sepsis / Q000276:immunology* / Q000401:mortality
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides