Model figure. (A) C. difficile toxins target the intestinal epithelium and cause severe pathology and gastrointestinal disease leading to morbidity and mortality. (B) When vaccinated mice are infected with C. difficile, IgG and IgA antitoxins protect mice from disease and inclusion of PPEP-1 and CdeM as immunogens enhances decolonization of toxigenic C. difficile from the gastrointestinal tract. Credit: Science (2024). DOI: 10.1126/science.adn4955
A large team of microbiologists, pathologists and infectious disease specialists affiliated with several institutions in the United States has developed an mRNA vaccine that has so far been shown to protect mice against intestinal bacterial infections with Clostridioides difficile .
In their article published in the journal ScienceThe group describes how they used mRNA technology to design a multipronged vaccine targeting several proteins needed by the bacteria to cause intestinal disease and its results when tested with mouse models.
Previous research has shown that hospitalized patients who receive antibiotics to treat various infections are left with vulnerable guts after the good bacteria in their gut is destroyed. This exposes them to bacterial infections such as C. difficile, which infects the intestine and releases toxins that cause a variety of illnesses, including diarrhea, severe cramping, and in some cases death from sepsis.
Medical researchers have been looking for ways to combat these bacteria, but until now the microbes have been able to evolve faster than the drugs used to kill them. In this new effort, researchers used lessons learned from research involved in developing vaccines against the virus that causes COVID-19 to develop one that could effectively combat C. difficile, at least in mouse models. .
The messenger RNA (mRNA) in vaccines used to fight COVID-19 involves causing human T cells to create proteins that indirectly interrupt the virus’s ability to attach to the cells they are trying to infect. The research team used mRNA to engineer several components of the immune system (immunoglobulins, T cells, and antibodies) to produce several types of proteins that could be used to fight C. difficile during different parts of its growth cycle. life, thus guaranteeing its effectiveness. by eliminating bacteria from a host.
In testing their vaccine, the researchers found that it was very effective: all mouse models given normally lethal doses of C. difficile recovered, while those in a control group all died. The researchers note that, like other mRNA vaccines, their vaccine does not prevent infection, but gives the immune system the means to fight it effectively.
More information:
Mohamad-Gabriel Alameh et al, A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection, Science (2024). DOI: 10.1126/science.adn4955
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Quote: Scientists develop mRNA vaccine that protects mice against gut bacteria C. difficile (October 6, 2024) retrieved October 6, 2024 from
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