Over the last decade, Clostridium difficile (C. difficile) infection has rapidly become more prevalent. C. difficile, often abbreviated as C. diff, usually spreads through hospitals and other healthcare facilities, and the elderly are particularly vulnerable. Our society’s overuse of antibiotics has been eliminating normal microbes, allowing C. difficile to take over. Infected patients then release bacterial spores and spread the pathogen to others.
Vaccines are a promising strategy to address this critical public health issue. They are a well-established form of medicine that could be utilized to prevent illness rather than treating an existing infection. While fecal transplants also are being explored, these treatments are very new, and clinicians do not yet know the long-term effects of such procedures.
Unique issues in vaccine development
One of the main challenges of developing vaccines is identifying the appropriate patient population. When a drug is intended as a treatment, sponsors can enroll patients with a certain disease or infection and determine whether the medication aids recovery. But preventative therapies such as vaccines must be tested on patients who are believed to be at high risk, such as the elderly, instead of people who are already infected. In such trials, proving efficacy is not as straightforward.
In addition, pathogens often mutate. Just as pharmaceutical companies continue to produce a new flu vaccine frequently to address genetic changes, developers may need to respond accordingly to C. difficile’s change. For example, the epidemic C. difficile strain BI/NAP1/027 emerged in the early 2000s; it appears to produce high levels of toxins A and B and a new toxin called binary toxin. Sponsors may need to perform additional molecular testing to identify mutations in the bacteria and continually evaluate the need for vaccine refinements.
Testing for C. difficile infection also requires unusual care. Extensive validation work at Covance has shown that the bacterium’s toxin degrades quickly at room temperature. Patients typically collect stool samples at home rather than in the clinic, and the sample must be properly stored until it is tested in the lab. To ensure robust results, detailed instructions must be provided, as well as containers that maintain the sample at the correct temperature during storage and transport.
Finally, regulatory guidelines for vaccine development are extremely stringent. Every deviation from the usual protocol must be monitored and documented, even changes as minor as using a different freezer or incubating a sample for an additional minute. Engaging an expert partner who is familiar with these requirements can ensure that these records are managed efficiently.
The value of a vaccine
The development of an effective vaccine could help prevent C. difficile from harming the patient even if the pathogen is present in the body. If approved, a vaccine could be administered to people who are at high risk for infections. These include elderly patients scheduled for surgery, nursing home residents, people who must frequently take antibiotics for chronic conditions and patients previously infected by C. difficile.
To conduct a successful vaccine trial, collaborating with a partner with deep experience in this therapeutic area is critical. Covance has managed more than 150 clinical trials for vaccines and immunotherapies and offers more than 3,000 assays to support vaccine development. Microbiology laboratories in Indianapolis, Geneva, Shanghai and Singapore can run C. difficile tests such as toxigenic cultures, susceptibility testing, toxin detection and the Cepheid GeneXpert® assay to detect the BI/NAP1/027 strain. Comprehensive validation work has allowed our experts to develop robust processes that ensure consistent and reliable results.
Discover how Covance can help make a difference in your Clostridium difficile (C. difficile) vaccine study. Read our white paper.