Clostridioides difficile

Content

Future Vaccines

In this chapter:

Introduction
Vaccines
References

Introduction

Clostridioides difficile (formerly Clostridium difficile) infection (CDI) is a major cause of antibiotic-associated diarrhoea and colitis and remains one of the most common pathogens in healthcare-associated infections. The spectrum of CDI ranges from asymptomatic carriage and mild diarrhoea to life-threatening pseudomembranous colitis, toxic megacolon, and fulminant colitis.

Long-term symptom resolution is difficult to achieve for many patients; approximately 20% experience recurrent infections after initially responding to therapy. Although traditionally associated with antibiotic use in healthcare settings, CDI has increasingly occurred in the community since the emergence of hypervirulent strains in the early 2000s.

CDI is mainly mediated by the protein exotoxins toxin A (TcdA) and toxin B (TcdB). Antibodies to TcdA and TcdB confer protection against primary and recurrent CDI.

Vaccines

Vaccine candidates targeting TcdA and TcdB may prevent clinical illness but do not prevent gastrointestinal tract colonisation. This has generated interest in targeting non-toxin pathogenic factors such as binary toxin (CDT), cell-surface antigens, spore-coat antigens, and flagella. Alternative C. difficile antigens show potential as immunogenic targets and novel pathways for vaccine development and are currently under pre-clinical investigation. Other considerations include the cross-reactivity of antibodies to antigens across different C. difficile strains, the need for the most suitable type of adjuvants, the optimal age for immunisation, demonstrating immune responses in high-risk elderly individuals, and the duration of protection.

Table 29.6 Clostridioides difficile candidate vaccines

References

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de Bruyn, G., Gordon, D. L., Steiner, T., et al. (2020). Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: A phase 3 multicentre, observer-blind, randomised, controlled trial. The Lancet Infectious Diseases https://doi.org/10.1016/S1473-3099(20)30331-5
de Bruyn, G., Saleh, J., Workman, D., et al. & H-030-012 Clinical Investigator Study Team (2016). Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial. Vaccine, 34(19), 2170–2178. https://doi.org/10.1016/j.vaccine.2016.03.028
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Donskey, C. J., Dubberke, E. R., Klein, N. P., et al. (2024). CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection. Clinical Infectious Diseases 79(6), 1503–1511. https://doi.org/10.1093/cid/ciae410
Vincent B. Young. (2025). Vaccinating against Clostridioides difficile Infection. N Engl J Med; 392:1237-1240. https://www.nejm.org/doi/full/10.1056/NEJMcibr2413794
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Riley, T.V.; Lyras, D.; Douce, G.R. (2019). Status of Vaccine Research and Development for Clostridium difficile. Vaccine, 37, 7300–7306. https://doi.org/10.1016/j.vaccine.2019.02.052
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