Özgür M Koc1,2,3, Philippe de Smedt4, Cécile Kremer5, Geert Robaeys2,3,6, Pierre van Damme4, Niel Hens5,7, Jorge Almeida8, Frank Falkenberg8,9, Paul Savelkoul1,10, Astrid Oude Lashof1. 1. Department of Medical Microbiology, School of NUTRIM, Maastricht UMC+, Maastricht, The Netherlands. 2. Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium. 3. Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium. 4. Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, Antwerp University, Antwerp, Belgium. 5. Data Science Institute, I-BioStat, Hasselt University, Hasselt, Belgium. 6. Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium. 7. Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, Antwerp University, Antwerp, Belgium. 8. CyTuVax B.V, Maastricht, The Netherlands. 9. CIRES GmbH, Dortmund, Germany. 10. Department of Medical Microbiology & Infection Control, Amsterdam University Medical Centers, VUMC, Amsterdam, The Netherlands.
Abstract
BACKGROUND & AIMS: Approximately 5%-10% of the general population respond inadequately to licensed recombinant hepatitis B vaccines. We assessed the immunogenicity and safety of a new HBAI20 vaccine, consisting of a new AI20 adjuvant (20-µg recombinant human IL-2 attached to 20-µg aluminium hydroxide) in combination with HBVaxPro®-10 µg. METHODS: In a double-blinded, randomised, controlled phase 2 trial, 18- to 59-year-old healthy non-responders (titre <10 mIU/ml after three or more doses ofhepatitis B vaccine) were assigned (3:1 ratio) to receive either HBAI20 vaccine orHBVaxPro®-10 µg in a 0, 1 and 2-month schedule. The primary outcome was seroprotection (titre ≥ 10 mIU/ml) measured 1-3 months following the third vaccination. RESULTS:A total of 133 participants were randomised to receive either HBAI20 vaccine (n = 101) or HBVaxPro®-10 µg (n = 32). In the modified intention-to-treat analysis, the seroprotection rate after the third vaccination was 92.0% (80/87) in the HBAI20 group and 79.3% (23/29) in the HBVaxPro®-10-µg group, P = .068. Using a generalised linear mixed model to adjust for stratification factors, a higher odds of seroprotection with HBAI20 vaccine was shown (adjusted odds ratio = 3.48, P = .028). Frequency of mild and moderate local adverse events was greater in the HBAI20 group than in the HBVaxPro®-10 µg. Rates of severe local adverse events and systemic adverse events were low and similar in both groups. CONCLUSIONS: In this group of hepatitis B vaccinenon-responders, the HBAI20 vaccine demonstrated a higher seroprotection rate when adjusting for stratification factors and a similar safety profile compared to the licensed recombinant HBVaxPro®-10 µg.
RCT Entities:
BACKGROUND & AIMS: Approximately 5%-10% of the general population respond inadequately to licensed recombinant hepatitis B vaccines. We assessed the immunogenicity and safety of a new HBAI20 vaccine, consisting of a new AI20 adjuvant (20-µg recombinant humanIL-2 attached to 20-µg aluminium hydroxide) in combination with HBVaxPro®-10 µg. METHODS: In a double-blinded, randomised, controlled phase 2 trial, 18- to 59-year-old healthy non-responders (titre <10 mIU/ml after three or more doses of hepatitis B vaccine) were assigned (3:1 ratio) to receive either HBAI20 vaccine or HBVaxPro®-10 µg in a 0, 1 and 2-month schedule. The primary outcome was seroprotection (titre ≥ 10 mIU/ml) measured 1-3 months following the third vaccination. RESULTS: A total of 133 participants were randomised to receive either HBAI20 vaccine (n = 101) or HBVaxPro®-10 µg (n = 32). In the modified intention-to-treat analysis, the seroprotection rate after the third vaccination was 92.0% (80/87) in the HBAI20 group and 79.3% (23/29) in the HBVaxPro®-10-µg group, P = .068. Using a generalised linear mixed model to adjust for stratification factors, a higher odds of seroprotection with HBAI20 vaccine was shown (adjusted odds ratio = 3.48, P = .028). Frequency of mild and moderate local adverse events was greater in the HBAI20 group than in the HBVaxPro®-10 µg. Rates of severe local adverse events and systemic adverse events were low and similar in both groups. CONCLUSIONS: In this group of hepatitis B vaccine non-responders, the HBAI20 vaccine demonstrated a higher seroprotection rate when adjusting for stratification factors and a similar safety profile compared to the licensed recombinant HBVaxPro®-10 µg.