The hemodynamic collapse of septic shock is the leading cause of death in critically ill patients and is the thirteenth leading cause of death overall in the United States, accounting for annual medical expenses approaching ten billion dollars. The bacterial component widely believed to be responsible for the induction of sepsis dung gram negative bacteremia is lipopolysaccharide (LPS). LPS stimulates the production of diverse inflammatory molecules which may ultimately mediate patient demise during sepsis. Therapies attempting to improve patient status following diagnosis of sepsis have been of limited value. This proposal attempts to develop an anti-idiotype vaccine capable of stimulating anti-LPS antibody titers. These antibodies may induce immunity to toxic effects of LPS by facilitating antibody-mediated clearance of LPS. Prophylactic vaccination with such a product should result in a substantial reduction in the incidence of sepsis. Monoclonal anti-LPS antibodies will be produced by immunizing mice with LPS and utilizing standard hybridoma technology. Anti-LPS will then be used to immunize mice to allow isolation of anti-id secreting hybridomas. Selected anti-ids will be administered to mice to stimulate synthesis of anti-anti-id antibodies. Immunized mice will be tested for resistance to LPS toxicity by observing survival following injection of LD100 doses of LPS.
