An mRNA vaccine protected mice against the deadly gut bacteria C. difficile

Clostridioides difficile is an extremely nasty intestinal bug, with few effective treatments and no approved vaccines. But the same technology that enabled the first COVID-19 vaccines has shown early promise in mouse experiments against the deadly infection, which kills 30,000 people in the United States each year.

An mRNA vaccine designed to target C. difficile and the toxins it produces protect mice from severe disease and death after exposure to lethal levels of the bacterial pathogen, researchers report Oct. 4. Science. While much more research will be needed to see if the vaccine is safe and effective in humans, the results hint that an mRNA vaccine could succeed where more conventional vaccines have failed.

C. difficile is an opportunistic pathogen that often wreaks havoc in the gut after a course of antibiotics wipes out healthy gut bacteria (SN: 24.10.18). The bacterium infects about 500,000 people in the United States each year, and the toxins it secretes can cause anything from mild diarrhea to sepsis and death. Once infected, it’s hard to beat, as antibiotic-resistant spores can stay in the body for years. Researchers have developed several different vaccines designed to induce the immune system to recognize C. difficile’toxins, but none have proven particularly effective.

A team of researchers at the University of Pennsylvania took a novel approach, using mRNA technology to design a multiplex vaccine that targets several underlying proteins. C. difficileits ability to cause disease. In laboratory mice and hamsters, the mRNA vaccine caused a stronger increase in a variety of immune cells – including antibodies, immunoglobulins and T cells – than traditional versions of the vaccine.

That broad immune response paid off. All vaccinated mice survived a highly lethal dose C. difficilethe study found, while all the unvaccinated mice died after a few days. Vaccinated mice still became infected, but experienced mild symptoms and quickly recovered. Immune protection was shown to be durable when the vaccinated mice were challenged with a second C. difficile The infection after six months went as well as in the first round.

Treatments that work in mice often fail in humans, although the researchers found that the mRNA vaccine induced an immune response in two rhesus macaques. However, the researchers acknowledge that these vaccines must be tested in “dirty mice,” which have more naturalistic immune systems than lab mice.SN: 20.4.16), before they are ready for human trials.

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Jonathan Lambert is a former staff writer for the biological sciences, covering everything from the origin of species to microbial ecology. He has a master’s degree in evolutionary biology from Cornell University.