Immune Aspects of Clostridioides difficile Infection and Vaccine Development

Infect Dis Clin North Am. 2025 Dec;39(4):801-820. doi: 10.1016/j.idc.2025.07.008. Epub 2025 Aug 12.

Abstract

Clostridioides difficile causes antibiotic-associated diarrhea and pseudomembranous colitis. The pathogenesis of C difficile infection is driven by 2 exotoxins, TcdA and TcdB, making them priority targets for therapeutic intervention. Several vaccine formulations targeting these toxins have reached phase 3 clinical trials, but none have successfully prevented colonization or disease. Recent advances in understanding C difficile pathogenesis and vaccinology have revitalized efforts to develop an effective vaccine. Here, we discuss basic and clinical research insights to provide a framework for developing next-generation C difficile vaccines.

Keywords: Clostridioidesdifficile; Mucosal immunity; Vaccines.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Proteins / immunology
  • Bacterial Toxins / immunology
  • Bacterial Vaccines* / immunology
  • Clostridioides difficile* / immunology
  • Clostridioides difficile* / pathogenicity
  • Clostridium Infections* / immunology
  • Clostridium Infections* / microbiology
  • Clostridium Infections* / prevention & control
  • Enterotoxins / immunology
  • Humans
  • Vaccine Development*

Substances

  • Bacterial Vaccines
  • Bacterial Toxins
  • Enterotoxins
  • Bacterial Proteins