Protection against experimental pseudomembranous colitis in gnotobiotic mice by use of monoclonal antibodies against Clostridium difficile toxin A

Abstract

The pathogenicity of Clostridium difficile is due to the production of two toxins (toxins A and B). We prepared monoclonal antibodies against toxin A and determined whether axenic mice passively immunized with the monoclonal antibodies were protected against C. difficile disease. The mice were kept in an isolator and were given ascites fluid intravenously prior to challenge with a toxinogenic strain of C. difficile. Control mice and mice receiving ascites fluid devoid of toxin antibody died within 2 days and had high levels of toxins A and B in their feces. Mice that received ascites fluid containing high amounts of toxin A monoclonal antibodies directed against the repeating units of the toxin survived. In protected mice, toxin B levels were similar to those in dying mice, but toxin A levels were greatly reduced. These data show that passive immunity induced by monoclonal antibodies against toxin A was effective against pseudomembranous cecitis.

Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract

“…Thus, the mechanism of protection is by toxin neutralization rather than prevention of C. difficile infection. Immunization of animals against toxin A alone may protect them from C. difficileinduced enterocolitis (6,19). In humans, however, toxin B also causes damage to the colonic mucosa (29).…”

“…Passive immunization also protects animals against C. difficile enterocolitis. Protection may be conferred by the parenteral administration of preformed antitoxin antibodies (1,6). Oral passive immunization is also effective, as evidenced by protection of infant hamsters after ingestion of breast milk from immunized mothers (19).…”

Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum

“…Inflammatory colitis and diarrhea associated with C. difficile are caused by release of two protein exotoxins, toxin A and toxin B (15,31). Although the intestinal mechanism of action of toxin A is not completely understood, binding of the toxin to its brush border receptor appears to be required for expression of enterotoxic effects (10,12,38). Injection of toxin A, a 308-kDa protein (11), into rodent intestine causes fluid secretion, increased mucosal permeability and mucosal damage, and release of inflammatory mediators (24,34,36,37).…”

Clostridium difficile Toxins Influence Hepatocyte Protein Synthesis Through the Interleukin 1 Receptor

“…LOSTRIDIUM DIFFICILE may produce fulminant infections through its 2 exotoxins, toxin A and toxin B. [1][2][3][4][5][6][7][8][9][10] Even though these infections are commonly localized to the colon, a significant systemic inflammatory response is usually apparent, characterized by high fever, neutrophilia, and the elaboration of acute-phase proteins.…”