Now that we have lowered the death rate of patients with gram negative bacteremia and septic shock by treatment with human antiserum to core lipopolysaccharide (LPS), we propose to extend these successful results by pursuing 3 specific aims: 1. To determine if J5 antiserum is an effective in preventing bacteremia and shock as it is in treating it. In these studies the antiserum would be given as prophylaxis to patients predisposed to bacteremia. In the first trial on prophylaxis with J5 antiserum we cut sharply the incidence of febrile attacks in neutropenic patients. We now propose to extent the trial by giving J5 antiserum to enough subjects to allow an evaluation of its efficacy against bacteremia as well. 2. To produce an effective, safe, human gamma globulin preparation for intravenous use in the treatment and prevention of gram negative bacteremia. Our goal during the period of this project is an IgM preparation that is free of non-specific anticomplementary activity but retains its ability to prevent and treat lethal bacteremia. After the effectiveness and safety of this preparation has been demonstrated in experimental animals, a new proposal will be submitted for a clinical trial of its safety and efficacy. 3. To produce in vitro human monoclonal antibody against core LPS and to test its ability to protect against experimental gram negative bacteremia and endotoxemia.
