Dissociation between Limulus neutralisation and in vivo protection in monoclonal antibodies directed against endotoxin core structures

Abstract

Studies with rough mutants of certain Gram-negative bacteria have indicated that monoclonal antibodies (mAbs) to endotoxin core can protect animals and man from endotoxic shock. We assessed the ability of such antibodies to neutralise endotoxin in the Limulus amoebocyte lysate (LAL) assay, and compared this to their protective effect in a murine model of endotoxic shock. We evaluated 11 mAbs raised against Salmonella minnesota R595. Endotoxin neutralisation in the LAL assay, expressed as 50% inhibition titres, ranged between 1/32 and 1/414. However, there was no apparent relationship between the titre required to produce 50% inhibition of LAL and its ability to protect mice from endotoxic shock. We conclude that LAL neutralisation appears unrelated to biological activity; in this system, LAL inhibition by mAb ascites cannot be used to predict protection in vivo.