The human gut contains a variety of bacteria and other microorganisms comprising the microbiome, and that’s a good thing! A healthy microbiome helps maintain a strong immune system and aids in digestion, among other important tasks. But sometimes, too much of a specific bacterium can result in infection, with the potential to progress from an ordinary health challenge to a life-threatening ordeal.

Clostridioides difficile, also known as C. difficile, is one such bacterium. It often exists relatively harmlessly in small amounts within our bodies, but when unregulated, it releases toxins that can sometimes cause severe diarrhea, intestinal perforation, sepsis, and even death in severe cases.

What Is C. difficile Infection?

In 2019, the U.S. Centers for Disease Control and Prevention categorized C. difficile as an urgent public health threati, its highest designation. C. difficile infection (CDI) is the cause of almost half a million infections per year in the U.S., most commonly among adults over the age of 65 and individuals with compromised immune systems or chronic health conditions.ii

While many CDI instances begin in hospitals or care facilities, where antibiotic use tends to be higher, about half occur in the community.iii Antibiotics can disrupt balance in the body’s microbiome and create conditions for the C. difficile bacteria to thrive.

The infection's unpredictability makes it particularly alarming, with outcomes ranging from mild diarrhea to potentially fatal complications. CDI can also recur in approximately 15 to 30 percent of patients, with the rate of recurrence continuing to increase with each incidence.iv

Leading the Charge: Pioneering Prevention of Severe CDI

While antibiotic use is a risk factor for the onset of CDI, antibiotics are currently the primary treatment for the infection, along with options like microbiome replacement therapy. Many experts believe a vaccine could help our immune systems fight the infection more effectively and efficiently, and may be able to reduce the need for further medical intervention.

Pfizer scientists are working to develop what could be the first vaccine against CDI, if successfully developed and approved. Using their extensive knowledge of the pathogen, cutting-edge vaccine technology, new diagnostic tools, and key learnings from previous clinical studies, the Pfizer team is advancing a novel vaccine candidate aimed at reducing disease caused by CDI.

Innovating for Success: Pfizer’s State-of-the-Art Research Program

“There are a number of unique aspects of this particular project from a scientific standpoint,” explains Ashlesh Murthy, Director, Bacterial Vaccines. “Our approach is to target and neutralize certain toxins produced by the bacterium, which we know are key drivers of disease. This is really state-of-the-art in the field.”

Ashlesh describes another significant innovation the team believes will contribute to a vaccine’s success: the addition of an adjuvant. Adjuvants are molecules designed to heighten the body’s innate immune response when administered alongside a vaccine antigen. They aim to attract immune cells to the injection site, allowing these cells to recognize the antigen more effectively and generate a stronger protective response. In some cases, adjuvants can also help reduce the number of doses needed to build an effective immune response.

Complementing their research on a vaccine itself, the team has also implemented highly sophisticated and sensitive diagnostic tools to monitor how the bacteria are responding to clinical candidates. “This two-step testing algorithm is an industry first,” says Michael Pride, Vice President, Bacterial Vaccines, “automating the processes that determine whether bacteria are present in clinical samples and, most importantly, whether they are producing the disease-causing toxins.”

Beyond the Statistics: Hope for the Future of CDI Care

Statistics around the prevalence and human impact of CDI are staggering, but the transformational potential of a vaccine extends far beyond these facts and figures. It represents a chance to help alleviate the constant stress and uncertainty faced by vulnerable populations. For people at risk, a successful vaccine could mean less worry about potential infection or reinfection when entering hospitals, staying in long-term care facilities, or taking antibiotics to manage other health concerns.

“Currently, there are no preventive vaccines available against C. difficile infection,” Ashlesh says. “What we have been able to achieve in advancing these clinical trials to the stage that they are is the closest that anybody has gotten to changing that.”

 

[i] 2019 AR Threats Report. CDC. Updated April 11, 2025. Accessed November 18, 2025. Available at: https://www.cdc.gov/drugresistance/biggest-threats.html.

[ii] About C. diff. CDC. Updated December 18, 2024. Accessed November 18, 2025. Available at: https://www.cdc.gov/c-diff/about/index.html.

[iii] Association of Clostridioides difficile infection rates with social determinants of health in Denver area census tracts, 2016–2019. Preventative Medicine Reports. Published December 2023. Accessed November 18, 2025. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10520868/.

[iv] Clostridioides Difficile: A Concise Review of Best Practices and Updates. Journal of Primary Care & Community Health. Published May 10, 2024. Accessed November 18, 2025. Available at: https://journals.sagepub.com/doi/10.1177/21501319241249645.