An mRNA vaccine candidate protects mice from Clostridioides difficile infection

The bacterium Clostridioides difficile causes about 500,000 infections in the US each year, according to the US Centers for Disease Control and Prevention. These infections inflame the colon, cause diarrhea, and can be deadly. Scientists have been working on vaccine candidates for C. difficile, but none have been approved by the US Food and Drug Administration. Now researchers report they can protect mice from C. difficile infections with a messenger RNA–lipid nanoparticle (mRNA-LNP) vaccine candidate (Science 2024, DOI: 10.1126/science.adn4955).

Researchers led by Mohamad-Gabriel Alameh, Drew Weissman, and Joseph P. Zackular at the University of Pennsylvania’s Perelman School of Medicine developed the system. The other vaccine candidates for the bacterial infection create antigens against only C. difficile protein toxins, but using the mRNA-LNP platform allows the researchers to target C. difficile’s entire life cycle by creating antigens to cellular and spore targets in addition to the bacterium’s protein toxins.

“Where the mRNA-LNP vaccine platform really shines is its ability to use multiple antigens,” Zackular says. What’s more, Alameh adds, the LNP delivery system is an excellent adjuvant that gives a boost to the body’s immune response.

Dan Peer, who studies molecular medicines at Tel Aviv University and was not involved in the research, says in an email that the mRNA-LNP platform “could provide a more potent alternative for preventing C. difficile infection, offering a promising new prophylactic strategy.”

The mRNA-LNP inoculation protected mice from an initial C. difficile infection and prevented recurrences in mice that already had an infection.

“We’re hopeful that not only could this vaccine be used to potentially protect patients that are at high risk but also it could help those who get stuck in that debilitating recurrent cycle” of C. difficile infection, Zackular says.

Next, the researchers would like to move the vaccine candidate into human clinical trials.