Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers

Background: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea and colitis and the most common pathogen of health care-associated infections. In the US, CDI causes approximately half a million infections and close to 30,000 deaths. Despite antibiotic treatment of C. difficile associated diarrhoea, the disease is complicated by its recurrence in up to 30% of patients. Methods: An open-label, partially randomized, dose-escalation Phase I trial was performed in two parts. Sixty volunteers aged >= 18 to <65 years were randomized into five treatment groups to receive three immunizations (Day 0, 7, 21) of VLA84 (20 mu g with Alum, 75 mu g with or without Alum, 200 mu g with or without Alum). Eighty-one volunteers aged >= 65 were randomized into four treatment groups (75 mu g with or without Alum, 200 mu g with or without Alum) and received four immunizations (Day 0, 7, 28 and 56). All subjects were followed for safety and immunogenicity for six months. Results: VLA84 was safe and well tolerated. Fifty-one adult volunteers (85%) and 50 elderly (62%) experienced at least one solicited or unsolicited adverse event (AE). Forty-eight adult volunteers (80%) and 40 elderly (49%) experienced related AEs which were mostly mild or moderate. No related serious adverse event and no death occurred. The vaccine induced high antibody titres against Toxin A and Toxin B in both study populations. Conclusion: VLA84 was safe, well tolerated and highly immunogenic in adult volunteers aged >= 18 to <65 years and elderly volunteers aged >= 65 years. (C) 2016 Elsevier Ltd. All rights reserved.