A multivalent mRNA-LNP vaccine protects against <i>Clostridioides difficile</i> infection
Mohamad‐Gabriel Alameh, Alexa Semon, Nile U. Bayard, Yi‐Gen Pan, Garima Dwivedi, James J. Knox, Rochelle C. Glover, Paula C. Rangel, Ceylan Tanes, Kyle Bittinger, Qianxuan She, Haitao Hu, Srinivasa Reddy Bonam, Jeffrey R. Maslanka, Paul J. Planet, Ahmed M. Moustafa, Benjamin Davis, Anik Chevrier, Mitchell Beattie, Houping Ni, Gabrielle S. Blizard, Emma E. Furth, Robert H. Mach, Marc Lavertu, Mark A. Sellmyer, Ying K. Tam, Michael C. Abt, Drew Weissman, Joseph P. Zackular
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.