Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study

• Published in: The Journal of infectious diseases Vol. 231; no. 3; pp. e511 - e520
• Main Authors: Leroux-Roels, Isabel, Alhatemi, Azhar, Caubet, Magalie, De Boever, Fien, de Wergifosse, Bertrand, El Idrissi, Mohamed, Ferreira, Guilherme S, Jacobs, Bart, Lambert, Axel, Morel, Sandra, Servais, Charlotte, Yarzabal, Juan Pablo
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 17.03.2025
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adjuvants, Vaccine - administration & dosage; Adjuvants, Vaccine - adverse effects; Adolescent; Adult; Aged; Antibodies, Bacterial - blood; Antigens, Bacterial - immunology; Bacterial Proteins - immunology; Bacterial Toxins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - adverse effects; Bacterial Vaccines - immunology; Clostridioides difficile - immunology; Clostridium Infections - immunology; Clostridium Infections - prevention & control; Enterotoxins - immunology; Female; Healthy Volunteers; Humans; Immunogenicity, Vaccine; Major; Male; Middle Aged; Placebos - administration & dosage; Young Adult; Clostridioides difficile; adjuvant; vaccine candidate; safety; immunogenicity
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiae466

This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B. In this first-in-human, phase 1, observer-blind study, subjects aged 18-45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50-70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose. Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation. The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile. NCT04026009.