Abstract
Clostridioides difficile infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine targeting C. difficile toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic C. difficile from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel C. difficile therapeutics with potential for limiting acute disease and promoting bacterial decolonization.
MeSH terms
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Animals
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology
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Bacterial Toxins* / genetics
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Bacterial Toxins* / immunology
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Bacterial Vaccines* / administration & dosage
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Bacterial Vaccines* / immunology
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Clostridioides difficile* / genetics
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Clostridioides difficile* / immunology
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Clostridium Infections* / immunology
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Clostridium Infections* / prevention & control
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Disease Models, Animal
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Female
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Gastrointestinal Microbiome
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Immunity, Cellular
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Immunity, Humoral
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Liposomes
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Mice
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Mice, Inbred C57BL
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Nanoparticles*
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RNA, Messenger / genetics
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Vaccines, Combined* / administration & dosage
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Vaccines, Combined* / immunology
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Virulence Factors / genetics
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Virulence Factors / immunology
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mRNA Vaccines* / administration & dosage
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mRNA Vaccines* / immunology
Substances
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Bacterial Proteins
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Bacterial Toxins
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Bacterial Vaccines
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Lipid Nanoparticles
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Liposomes
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mRNA Vaccines
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RNA, Messenger
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Virulence Factors
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Vaccines, Combined