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We might soon have a way to prevent one of the world’s most debilitating and hard-to-treat infections in the world. Scientists are developing a cutting-edge vaccine that could stop Clostridioides difficile—a bacteria known for causing severe gut infections—in its tracks.
Scientists detailed their development of an experimental vaccine candidate for C. difficile bacteria, better known as C. diff, in new research this week. The vaccine is based on the same mRNA technology used to create some of the first widely available covid-19 vaccines.
While many people carry C. diff in their guts without issue, the bacteria can sometimes grow out of control, triggering diarrhea and colitis (a common trigger for this is antibiotic use, since the drugs can kill off harmless bacteria that keep C. diff in check). Antibiotics can treat these initial infections, but about one in six people will then experience recurrent bouts of C. diff that often prove even harder to clear. So scientists have long hoped to find a way to short circuit this miserable cycle from happening in the first place, such as through an effective vaccine.
Researchers at the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) developed the vaccine candidate, which leverages mRNA technology to target C. diff at different key points. These bacteria can shapeshift and use a variety of tricks to ensure their survival. They can turn into long-lasting spores that bide their time hiding in the soil, for instance, or combine en masse into a hardy biofilm in our guts that allow them to resist antibiotics. Pathogenic C. diff strains also produce toxins that make it easier for them to continue growing but at the cost of sickening us. The team’s vaccine is intended to train our immune system against several toxins and other virulence factors of C. diff that make it such a menace.
So far, their plan appears to be working as hoped, at least in mice. The vaccine provided mice long-lasting protection against both the primary and recurrent forms of C. diff infection, the researchers found. They also tested an upgraded version of the vaccine, designed to help the body recognize non-toxin cellular and spore antigens of C. diff, and found that it improved the mice’s ability to clear toxin-producing bacteria from the gut. The team’s findings were published this month in the journal Science.
“Our approach was to create a multivalent mRNA vaccine that would attack multiple aspects of C. diff’s complex lifestyle simultaneously without affecting the normal microbiota,” said co-lead author Mohamad-Gabriel Alameh, an assistant professor of Pathology and Laboratory Medicine at Penn and a senior principal scientist at CHOP, in a statement from the university.
This research is still in the early stages of development, of course, so it’s no guarantee that the team’s vaccine will work just as well in people. But a C. diff vaccine, if successfully developed, would have a tremendous health impact. It’s estimated that nearly half a million C. diff infections occur in the U.S. every year, which can be especially dangerous and sometimes deadly for already vulnerable populations, such as elderly people or those in the hospital for other conditions. Annually, it’s thought around 30,000 people die from C. diff every year. Recent research shows that C. diff is becoming more of a problem outside of hospitals, too.
It will likely take years for this vaccine to reach large-scale trials even if things continue to go well. But the future overall is already looking bright for mRNA-based vaccines. Following the rollout of the covid-19 vaccines, Moderna’s mRNA vaccine for respiratory syncytial virus (RSV) was approved by the Food and Drug Administration just this past May. mRNA vaccines for cytomegalovirus, the flu, and some cancers are now close to fruition as well.
