A direct enzyme-linked immunosorbent assay (Elisa) for antibodies to enterobacterial score glycolipid and lipid A. Results in Healthy Subjects and in Patients Infected by Gram-Negative Bacteria

We have developed an ELISA for IgM and IgG antibodies to the core glycolipid (CGL) of the Re mutant Salmonella minnesota R 595, and to lipid A. Anti-CGL antibodies have been detected in sera from 37% of healthy blood donors, whereas anti-lipid A activities were found in 13% of individuals only. The anti-CGL and anti-lipid A activities were examined in patients in a surgical intensive care unit, selected on the basis of a definite risk of infectious complications due to Gram-negative bacteria. Of the patients who developed such infections, the rate of favourable outcome was significantly higher in patients with either stable positive or increasing anti-CGL activities than in patients found to be negative. Our results provide clear evidence that anti-CGL antibodies contribute to host defence against various Gram-negative bacteria

Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock

The role of anti-endotoxin antibodies in the management of gram-negative bacteremia and the experimental and clinical studies on the cross-protection afforded by core LPS antibodies are reviewed. These studies did not achieve clarification of the epitope(s) and effector mechanism(s) involved in protection. Recently, two anti-lipid A IgM monoclonal antibodies, designated E5 and HA-1A, have been investigated in patients with gram-negative bacterial infections and clinical manifestations of septicemia. E5 reduced the mortality of patients if they were not in shock, whether they were bacteremic or not. A confirmatory study has been initiated. In contrast to E5, HA-1A protected patients whether they were in shock or not, but only when they were bacteremic at randomization. Although these studies suggest beneficial effects, the type of patients who may benefit from this expensive therapy should be further defined. Further investigations are needed to clarify the mechanisms of protection of these antibodies