Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens
Stevens, Dennis L.
Titball, Richard W.
Bayer, Clifford R.
Hayes-Schroer, Susan M.
Bryant, Amy E.
University of Exeter (at the time of publication Richard Titball was at the Defence, Science and Technology Laboratory, Salisbury, UK); Veterans Affairs Medical Center, Boise, US; University of Idaho; Defence, Science and Technology Laboratory; University of Washington
The Journal of Infectious Diseases
Published by University of Chicago Press for the Infectious Diseases Society of America
Clostridium perfringens gas gangrene is characterized by rapid tissue destruction, impaired host response, and, often, death. Phospholipase C (α-toxin) is the virulence factor most responsible for these pathologies. The present study investigated the efficacy of active immunization with the C-terminal domain of α-toxin (Cpa247–370) in a murine model of gas gangrene. Primary end points of the study were survival, progression of infection, and tissue perfusion. Secondary end points, which were based on findings of histologic evaluation of tissues, included the extent of tissue destruction and microvascular thrombosis, as well as the magnitude of the tissue inflammatory response. Survival among C-domain–immunized animals was significantly greater than that among sham-immunized control animals. Furthermore, immunization with the C-domain localized the infection and prevented ischemia of the feet. Histopathologic findings demonstrated limited muscle necrosis, reduced microvascular thrombosis, and enhanced granulocytic influx in C-domain–immunized mice. We conclude that immunization with the C-domain of phospholipase C is a viable strategy for the prevention of morbidity and mortality associated with C. perfringens gas gangrene.
© 2004 by the Infectious Diseases Society of America. All rights reserved.
190 (4), pp. 767-773