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A new vaccine offers hope for treating and even preventing the highly contagious and difficult-to-treat Clostridioides difficile infection (commonly known as C. difficile or C. difficile). In animal models, this first mRNA-LNP C. difficile vaccine protects against primary and recurrent C. difficile infections by inducing a strong immune response and eliminating existing C. difficile bacteria from the intestine. It has been found to promote and even overcome infectious diseases. Researchers at the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia say the animals lack the host immunity that protects them after infection. The results, published in the journal Science, pave the way for clinical trials of the vaccine.
C. difficile is a bacterium that can cause infections with symptoms ranging from diarrhea to fatal colon damage. The virus spreads quickly through spores that are difficult to kill and commonly infects vulnerable populations such as the elderly, children, people taking antibiotics, and even patients in hospitals and nursing homes. . The bug is also persistent, with 30 to 40 percent of people diagnosed with C. difficile infection likely to become infected again. There is currently no C. difficile vaccine available, and the main treatment for the infection is long-term antibiotic therapy. However, because antibiotics also target beneficial bacteria within the gut microbiome, C. difficile takes advantage of the absence of antibiotics to release toxins into the colon, allowing C. difficile to multiply.
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“Our approach was to create a multivalent mRNA vaccine that simultaneously attacks multiple aspects of C. diff’s complex lifestyle without affecting the normal microbiome,” said co-first author said Dr. Mohammad Gabriel Alameh, assistant professor of pathology and laboratory medicine at . Penn and senior chief scientist at Children’s Hospital of Philadelphia. “Antibiotics are not always an effective tool in successfully treating very tough pathogens like C. diff. It has only just begun to show itself.”
“While most vaccines prompt the immune system to produce specific antibodies, mRNA vaccines can be easily packaged to allow the immune system to do multiple things to protect against the bacteria, making Clostridium difficile vaccines more effective. It was the perfect candidate: a virus or a fungus,” said study author and Nobel laureate Drew Weissman, M.D., Roberts Family Professor of Vaccine Research at Penn, whose work laid the basis for the world’s first mRNA vaccine. Built.
“C. diff can persist in many forms in the gut, including biofilms and incredibly tough spores, making it extremely difficult to treat,” said Co-Director of the CHOP Center for Microbial Medicine. said Dr. Joseph P. Sackler, assistant professor. Penn Professor of Pathology and Laboratory Medicine. “This study demonstrates that collaboration between vaccine researchers and basic scientists can turn new discoveries into potential treatments faster than ever before.”
The researchers used an mRNA-LNP vaccine platform, the same platform that provided the highly effective mRNA COVID-19 vaccine. Although many of the mRNA vaccines being studied are for viruses, this pioneering technology has broader applications than other vaccine designs, such as inactivated vaccines. A successful C. difficile vaccine would mark a turning point in C. difficile treatment research, which has struggled to achieve breakthroughs against this difficult pathogen. Previous vaccines, including a non-mRNA vaccine that was in clinical trials in 2022, did not meet the standards for research to be brought to market. “The mRNA-LNP vaccine has provided us with a new tool to fight complex bacterial infections like C. diff, a problem that is becoming even bigger with increasing antimicrobial resistance. ,” said Alexa Siemon, co-lead author of the study. PhD candidate at the University of Pennsylvania.
This research further strengthens Philadelphia’s growing field of mRNA research. Penn has designed mRNA vaccines to prevent Lyme disease, norovirus, and herpes simplex virus 2. Penn is also researching how mRNA could treat sickle cell disease, deadly food allergies, and even treatments. Cancer among other diseases. CHOP develops novel ionized lipids and biomaterials for vaccine and gene therapy applications in perinatal and pediatric medicine, extending the success of its mRNA-LNP platform for use in the treatment of glycogen storage disease type 1a (GSD1a) We are researching possible mRNA vaccines and therapeutic drugs. In addition to isolated methylmalonic acidemia, research continues into various forms of cancer and bacterial infections that are difficult to treat.
References: Alameh MG, Semon A, Bayard NU, et al. Multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection. Science. 2024;386(6717):69-75. doi: 10.1126/science.adn4955
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