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A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection

Affiliations
  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 2Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 3Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
  • 4Division of Protective Immunity, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
  • 5Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 6Division of Infectious Disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 7Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
  • 8The Center for Microbial Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
  • 9Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 10Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 11Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • 12Division of Pediatric Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
  • 13Comparative Genomics, American Museum of Natural History, New York, NY, USA.
  • 14Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
  • 15Acuitas Therapeutics, Vancouver, British Columbia, Canada.
  • 16Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 17Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Published on:

October 3, 2024

Abstract

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 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 from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel therapeutics with potential for limiting acute disease and promoting bacterial decolonization.