Scientists have developed an experimental vaccine against the diarrhea causing bacterium Clostridium difficile that not only induced a strong immune response in animal models, but also protected 100% of mice from an otherwise lethal dose of the bacterial toxins. The researchers are hopeful that with further development, this vaccine could represent a safe and effective way to curb disease caused by this organism. The study has been published in Infection and Immunity.
C. difficile infection is responsible for the vast majority of hospital-acquired diarrhea in developed nations. While this bacterium is found in the gut of up to 3% of healthy adults and 66% of infants, it’s usually kept in check by other intestinal residents and thus does not cause disease. However, if the balance of bacteria in the gut is disturbed, for example by antibiotics, this organism can quickly cause disease.
C. difficile is a spore former and these can survive for weeks, or even months, on surfaces and clothes, giving ample opportunity for spread which is usually facilitated by the hands of healthcare workers. Disease is mediated by the effects of two different toxins produced by the bacterium- toxin A and toxin B. Some individuals produce a strong antibody response to parts of these toxins which prevents the onset of disease. In particular, antibodies that target a specific region used to bind to host cell receptors are very effective at neutralizing these toxins.
Armed with this knowledge, the researchers developed a DNA vaccine that encodes the receptor binding domains of the toxins. They then immunized mice and non-human primates with the resulting vaccine which stimulated the production of both specific antibodies against these regions and antibody-secreting cells. When researchers took sera from these immunized animals, they found that it could neutralize purified toxins in cells in the lab.
Furthermore, just two doses of the vaccine protected mice against an otherwise lethal dose of purified C. difficile toxins. According to lead author Michele Kutzler, this is important because of the relatively short window between C. difficile colonization and the onset of disease symptoms.
Finally, the researchers also tested the efficacy of the vaccine against mice challenged with spores from epidemic strains and it was found to provide significant protection.
The researchers are encouraged by these impressive results and would like to pursue human studies when the vaccine is fully developed. If the vaccine proves to be safe and effective, it would be extremely useful given the fact that treating recurrent disease is particularly difficult. Mortality and morbidity rates have also risen over the last decade which is likely facilitated by the emergence of hypervirulent strains. Consequently, it’s estimated that C. difficile costs the US around $10 billion annually, a cost that could be dramatically cut with the development of an effective vaccine.
