Phase 1 Trial of Adjuvanted Clostridioides difficile Vaccine Candidate in Adults

Overview

This phase 1 randomized placebo-controlled study evaluated the safety and immunogenicity of a Clostridioides difficile vaccine candidate containing the F2 antigen with or without the AS01 adjuvant in healthy adults. The vaccine was well tolerated, with mostly mild to moderate transient adverse events, and elicited a stronger immune response when administered with the AS01 adjuvant. A third dose further enhanced immune responses in subjects with low baseline neutralization titers.

Background

Clostridioides difficile infection (CDI) is a significant cause of healthcare-associated diarrhea and can lead to severe complications. Current treatments rely on antibiotics, but recurrence rates remain high, especially in older adults. Immunization targeting the main toxins A and B produced by C. difficile offers a promising preventive strategy. The GSK vaccine candidate uses the F2 antigen, a fusion protein of toxin binding domains, combined with the AS01 adjuvant to enhance immune responses.

Data Highlights

Key Findings

• The vaccine candidate was well tolerated with no serious adverse events related to vaccination.
• Solicited adverse events such as injection site pain, tiredness, and headache were mostly mild to moderate and transient, occurring more frequently in the adjuvanted group.
• Immunogenicity, measured by neutralization activity against toxins A and B, was significantly higher in subjects receiving the F2 antigen with AS01 adjuvant compared to antigen alone.
• A third dose administered approximately 15 months later boosted immune responses in subjects with low baseline neutralization titers.
• The AS01 adjuvant effectively enhanced the vaccine's immunogenicity, consistent with its known effects in other vaccines.

Clinical Implications

The favorable safety profile and enhanced immunogenicity of the adjuvanted vaccine candidate support further clinical development for prevention of CDI, particularly in older adults at higher risk. The ability of a third dose to boost immunity in low responders suggests potential for tailored vaccination schedules. Monitoring for reactogenicity remains important, especially with adjuvanted formulations.

Conclusion

This first-in-human study demonstrates that the GSK Clostridioides difficile vaccine candidate, especially when combined with the AS01 adjuvant, is safe and elicits strong neutralizing immune responses against key toxins. These results provide a foundation for advancing this vaccine in clinical development to address the significant burden of CDI.

References

1. GSK Phase 1 Study NCT04026009 -- Evaluation of Safety and Immune Response of an Adjuvanted Clostridioides difficile Vaccine Candidate