EVALUATION OF PROTECTION BY 2 ENDOTOXIN-NEUTRALIZING IGM MONOCLONAL-ANTIBODIES IN DIFFERENT PERITONITIS MODELS

Two anti-core glycolipid (CGL) IgM monoclonal antibodies (mAbs 8-2 and 26-20), previously shown to display cross-reactivity with heterologou s lipopolysaccharide (LPS) in vitro and to provide cross-protectivity against endotoxin challenge in vivo, were evaluated for their potentia l to protect mice against death from peritonitis caused by heterologou s bacterial challenge. Without concurrent antibiotic treatment neither antibody was protective. Compared with a control mAb, prophylactic tr eatment with mAb 8-2 significantly increased the survival of gentamici n-treated mice challenged with the rough strain Salmonella minnesota R e595. Both mAb 8-2 and a control mAb, in combination with a suboptimal dose of ceftazidime, increased survival following challenge with the clinical isolate Escherichia coil O7:K1. In a model of mucin-enhanced peritonitis, neither mAb was protective against challenge with inocula of E. coil O7:K1, ranging from 10(2) to 10(4) bacteria. We conclude t hat protection of mice by anti-CGL mAb 8-2 against heterologous challe nge is vitally dependent on concurrent treatment with antibiotics and that protection may not be attributable to the anti-CGL specificity of these antibodies.