A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection

• 成果类型: Article
• 署名作者: Alameh, Mohamad-Gabriel; Semon, Alexa; Bayard, Nile U.; Pan, Yi-Gen; Dwivedi, Garima; Knox, James; Glover, Rochelle C.; Rangel, Paula C.; Tanes, Ceylan; Bittinger, Kyle; She, Qianxuan; Hu, Haitao; Bonam, Srinivasa Reddy; Maslanka, Jeffrey R.; Planet, Paul J.; Moustafa, Ahmed M.; Davis, Benjamin; Chevrier, Anik; Beattie, Mitchell; Ni, Houping; Blizard, Gabrielle; Furth, Emma E.; Mach, Robert H.; Lavertu, Marc; Sellmyer, Mark A.; Tam, Ying; Abt, Michael C.; Weissman, Drew; Zackular, Joseph P.
• 署名单位: University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; University of Texas System; University of Texas Medical Branch Galveston; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; American Museum of Natural History (AMNH); Universite de Montreal; Polytechnique Montreal; University of Pennsylvania; University of Pennsylvania
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12428
• DOI: 10.1126/science.adn4955
• 发表日期: 2024-10-04
• 页码: 69-75
• 关键词: t-cells; pathogenesis; resistance; microbiota

摘要

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.