Safety and immunogenicity of Clostridium difficile toxoid vaccine in Japanese adults

• Published in: Human vaccines & immunotherapeutics Vol. 14; no. 2; pp. 322 - 328
• Main Authors: Matsuoka, Osamu, Patel, Dhaval M., Sasaki, Shin, Oka, Hayato, Sasaki, Toru, Pietrobon, Patricia J., Laot, Thelma, Bouckenooghe, Alain, Menezes, Josemund, de Bruyn, Guy
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.02.2018; Taylor & Francis Group
• Subjects: Adult; Aged; Antibodies, Bacterial - blood; Asian Continental Ancestry Group; Bacterial Toxins - immunology; Clostridium difficile; Clostridium difficile - immunology; Clostridium difficile - metabolism; Clostridium Infections - prevention & control; Female; Humans; immunogenicity; Male; Middle Aged; Research Paper; safety; Seroconversion; vaccine; vaccine; safety; immunogenicity; Clostridium difficile
• DOI: 10.1080/21645515.2017.1395538
• ISSN: 2164-5515

This was a randomized, placebo-controlled, Phase I/II study conducted in a Japanese cohort to assess the safety and immunogenicity of Clostridium difficile vaccine (the same formulation as that used in the ongoing global Phase III study). Healthy Japanese adults aged 40-75 years were randomized to receive either C. difficile vaccine (N = 67) or placebo (N = 34) by intramuscular injection on Days 0, 7, and 30. Serum IgG specific for toxins A and B was measured by enzyme-linked immunosorbent assay (ELISA) and in vitro functional activity by toxin neutralizing assay (TNA). The seroconversion rate (percentage of participants with a ≥4-fold rise in antibody levels from baseline) was high for both toxin A (ELISA and TNA) and toxin B (ELISA), approaching 100% for each by Day 60. For toxin B assessed by TNA, however, the response was lower, with the seroconversion rate not rising significantly beyond the value of 42.9% seen on Day 14 (44.4% at Day 60). Although the response in the participants who were seronegative at baseline was slower than that in those who were seropositive, seroconversion was seen in nearly all (100%) subjects by Day 60, with the exception of the response to toxin B evaluated using TNA (16-18% on Days 14-60). The proportion of participants with solicited local reactions, solicited systemic reactions, and vaccine-related unsolicited reactions were 67.6%, 19.1%, and 20.6%, respectively. Most of the adverse reactions were mild to moderate in intensity, occurring within 3 days post-vaccination, and resolving by 3-6 days post-vaccination. There were no withdrawals due to adverse events and no serious adverse events. These data confirm the safety and immunogenicity of C. difficile vaccine in Japanese adults.