Bivalent C. difficile vaccine safe, well tolerated in older adults
An investigational bivalent Clostridium difficile vaccine that contains equal dosages of genetically and chemically detoxified toxins A and B has a tolerable safety profile and is immunogenic in healthy older adults, according to the results of a phase II trial.
The trial randomized 855 healthy adults aged 65-85 years to receive vaccine (100 or 200 μg) or placebo at 0, 1 and 6 months (month regimen) or 1, 8 and 30 days (day regimen).
Researchers assessed the safety, tolerability and immunogenicity of the vaccine by measuring serum toxin A- and B-specific neutralizing antibodies. They also recorded participant-reported local reactions (LRs) and systemic events (SEs), adverse events (AEs), serious AEs, newly diagnosed chronic medical conditions, and immediate AEs.
Immune responses were higher in the 200- vs 100-µg dose group across regimens. Compared with the day regimen, the month regimen produced stronger and more persistent immune responses, which remained elevated 12 months after the third dose. Responses peaked at month 7 in the month-regimen group and at day 37 in the day-regimen group.
More patients in the vaccine groups than in the control groups reported LRs (primarily injection site pain), while SE incidence was similar across groups. AEs occurred with greater frequency in the day-regimen group than in the month-regimen group.
The findings demonstrate encouraging tolerability and immunogenicity of the C. difficile vaccine, supporting its continued development for C. difficile infection prevention in older adults, the researchers said, adding that the 200-μg dose vaccine was selected for development in ongoing phase III studies.