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The Future of Infection Control: mRNA Vaccines for C. diff

Clostridiodes difficile, more commonly called C. diff is a bacteria many people carry in their gut without issue. However, if given the chance to grow out of control, it can cause one of the world’s most debilitating and hard-to-treat infections. An estimated half a million cases of C. diff infections occur in the U.S. every year, and around 30,000 of those affected die. Creating a widespread and accessible vaccine against this bacterial infection would help protect those in vulnerable populations and reduce others from spreading it.

C. diff infections often occur during or shortly after using antibiotics to treat another condition. This is because antibiotics work by killing the bad bacteria in the body that cause harm, but they can also kill the good bacteria that protect the body from infection. This allows C. diff bacteria already present in the body to thrive and replicate. Outside our body, the C. diff bacteria spreads through spores. Spores are inactive forms of the bacteria with a protective layer that allows them to live for years on surfaces and in the soil. When the spores from the environment are swallowed they become active again and typically infect vulnerable populations like the elderly, children, and patients in hospitals or nursing homes. Even individuals with none of these risk factors may develop an infection.

When someone is infected with C. diff, it causes symptoms of diarrhea and dehydration and in more severe cases can lead to colon inflammation, serious intestinal conditions, or even death. Due to the bacteria’s persistent nature, the infection may return multiple times. Approximately 30-40% of individuals diagnosed with C. diff will likely get it again. Joseph P. Zackular, PhD, co-director of the Center for Microbial Medicine at the Children’s Hospital of Philidelphia (CHOP) and an assistant professor of Pathology and Laboratory Medicine Penn, explains that C. diff can persist in different forms in the gut, including communities of bacteria called biofilms, or as spores waiting to infect again. These forms are what make the infection so difficult to treat. Currently, the most common treatment for C. diff is antibiotics. However, because antibiotics also target good bacteria in the gut, C. diff often takes advantage of this and grows into a large colony. Once colonized, C. diff releases toxins into the colon that help the bacteria defend itself by actively damaging the immune cells trying to fight C. diff. They also hurt the body by causing excess fluid secretion and inflammation in the gut, which leads to symptoms such as watery stool and sometimes complications like colitis (inflamed colon and/or large intestine). These conditions in the gut decrease the body’s ability to keep the bacteria at bay and allow C. diff to thrive and repeat the cycle.

Due to recent testing and research done by Penn Medicine and the Children’s Hospital of Philadelphia, scientists are making steps toward a vaccine to protect individuals from C. diff infections. The researchers aimed to create a vaccine that attacks the bacteria’s complex behavior without harming the gut microbiome (environment of the gut). This vaccine was created using the same mRNA-LPN technology that built the first widespread and effective COVID-19 vaccines. It targets the bacteria at different key points and trains our immune systems against some of C. diff’s toxins and other factors that make it difficult to treat. Researchers stated that the immune cell response “increased with vaccine dose and [was] significantly higher” than with other traditional vaccines.

Testing of this vaccine has proven to be successful in trials done on mice. An upgraded version of the vaccine was also tested and results showed that it improved the mice’s ability to rid the gut of the C. diff and toxins. Though it’s in the early stages of development, researchers state that the results pave the way for human trials. While there’s no guarantee that the vaccine will work as well in people, if it’s successful it would greatly impact the health of communities. “This work represents how collaboration between vaccine researchers and basic scientists can transform new discoveries into potential therapeutics faster than ever before,” said Joseph P. Zackular. While it will likely take years for the vaccine to reach large-scale trials, this is a big step toward the bright future of mRNA vaccines!

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