Could a vaccine help prevent infection with Clostridium difficile (C difficile), which causes thousands of deaths every year? In a first-in-human phase 1 study, researchers compared 3 doses of an investigational vaccine with placebo. The vaccine consisted of toxoids A and B (the principle virulence factors of C difficile-associated disease), and given with or without aluminum hydroxide in doses of 50, 100, or 200 μg at 0, 1, and 6 months.
The vaccine was well tolerated and effective. Local reactions and systemic events—mostly injection site pain, headache, and fatigue—were predominantly mild to moderate. Increasing the dosage or number of doses did not affect the frequency and severity of adverse effects, as reported by the participants in e-diaries.
Both the toxin A- and toxin B-specific neutralizing antibody levels increased from baseline. The first dose produced “modest” increases, but the second dose produced “marked” increases and the third dose had a “substantial” booster response, the researchers say. The booster response against toxin A was similar in both age groups tested (50-64 years and 65-85 years); the response against toxin B was the same or slightly higher in the older group.
Overall, antibody responses were higher in the toxoid-only groups. The researchers note that aluminum salts have been used to enhance vaccine responses for decades and it was somewhat unexpected in this study that the toxoid-only vaccine led to better antibody responses.
While the study was limited by the small number of participants, the researchers say, the robust response and persistence of immune response to 12 months support further investigation.
Source: Sheldon E, Kitchin N, Peng Y, et al. Vaccine. 2016;34(18):2082-2091 doi: 10.1016/j.vaccine.2016.03.010