Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination

Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Su Wang, Richard R. Rustandi, Catherine Lancaster, Laura G. Hong, David S. Thiriot, Jinfu Xie, Susan Secore, Adam Kristopeit, Sheng-ching Wang, Jon H. Heinrichs
Clostridium difficile is the leading cause of hospital-acquired diarrhea, also known as C. difficile associated diarrhea. The two major toxins, toxin A and toxin B are produced by most C. difficile bacteria, but some strains, such as BI/NAP1/027 isolates, produce a third toxin called binary toxin. The precise biological role of binary toxin is not clear but it has been shown to be a cytotoxin for Vero cells. We evaluated the toxicity of these toxins in mice and hamsters and found that binary toxin causes death in both animals similar to toxins A and B. Furthermore, immunization of mice with mutant toxoids of all three toxins provided protection upon challenge with native toxins. These results support the concept that binary toxin contributes to the pathogenicity of C. difficile and provide a method for monitoring the toxicity of binary toxin components in vaccines.



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