Abstract

The ability of antisera against lipopolysaccharide (LPS) raised by immunization with gram-negative bacteria to prevent LPS toxicity and death from gram-negative bacteremia is well established. To demonstrate conclusively that the protective antibody is specific for LPS, we tested an anti-LPS monoclonal antibody (mAb) in three animal models. 7G is an IgG3 mAb directed against an oligosaccharide side chain determinant of LPS from E. coli 0111:B4. This anti-LPS mAb increased the LD50 of 0111:B4 LPS in mice and protected rabbits against the dermal Shwartzman reaction elicited by 0111:B4 LPS. 7G mAb also protected mice against lethal infection with mucin-enhanced E. coli 0111:B4. Pretreatment with 250 micrograms of 7G increased the LD50 by more than 1.5 logs. These studies prove that oligosaccharide side chain-specific antibody to LPS confers protection against LPS toxicity in vivo and against experimental gram-negative infection. In addition, these studies suggest the potential of anti-LPS monoclonal antibody as therapy for gram-negative infection.