Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection.
Previous experimental and clinical studies have demonstrated the ability of polyclonal antibody directed against the core lipopolysaccharide (LPS)-lipid A component of endotoxin to reduce mortality. We sought to characterize the ability of a single murine monoclonal IgG1 antibody (8A1 MAb) to react to a variety of gram-negative microorganisms, to promote phagocytosis, and to provide protection during experimental murine sepsis. The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS antigens examined by enzyme-linked immunosorbent assay. Reactivity was highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was promoted by this monoclonal antibody to several gram-negative bacteria, except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced survival during bacteremia due to either Escherichia coli 0111:B4 or Klebsiella pneumoniae, and during endotoxemia due to all types of LPS examined except P aeruginosa. We concluded that a single MAb with anti-lipid A specificity was cross reactive in vitro and cross protective in vivo. A clinical trial comparing polyclonal and monoclonal antibody in high-risk septic patients seems warranted.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006090:Gram-Negative Bacteria / Q000276:immunology*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D051379:Mice; D010587:Phagocytosis; D018805:Sepsis / Q000276:immunology / Q000401:mortality / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D008070:Lipopolysaccharides