TY - JOUR
T1 - Serological response to three alternative series of hepatitis B revaccination Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders
T2 - a multicentre, open-label, randomised, controlled, superiority trial
AU - Raven, Stijn F. H.
AU - Hoebe, Christian J. P. A.
AU - Vossen, Ann C. T. M.
AU - Visser, Leo G.
AU - Hautvast, Jeannine L. A.
AU - Roukens, Anna H. E.
AU - van Steenbergen, Jim E.
N1 - Funding Information:
For the RESPONS trial, at publication of related articles, data will be made available to the public. Owing to the privacy and intellectual property rights legislation, published data will in principle be anonymised/deidentified participant data, including the metadata and documentation necessary for the discovery and correct interpretation of the data. This contributes to the FAIRness of the project data. Data will be made available via Radboud University's RIS interface to the public in the CoreTrustSeal certified DANS EASY archive . The DANS EASY archive is based on Dublin Core metadata and includes the assignment of a persistent identifier (DOI) to the data. Data will be available for the long term, at least for the required 10 years set by the Radboud University Research Data Management policy . Data will be made available via a Restricted Access licence (automated access on request via DANS EASY, by signing a data use agreement to guarantee the correct reuse of the data). Acknowledgments This investigator-initiated study received funding from a non-profit independent governmental organisation—namely, the National Institute for Public Health and the Environment (numbers 212-11, 213-11, 214-11, and 215-11). Employees of the National Institute for Public Health and the Environment were involved in the study design, data analysis, interpretation of the results, and writing of the report. GlaxoSmithKline and Merck Sharp & Dohme provided the vaccines used in this study. Neither manufacturer was involved in the study design, data collection, data analysis, interpretation of the results, or writing of the report. We thank all the participating centres for their support; Marita Werner, and Marga Smit at the South Limburg Public Health Service; Mieke Croughs, and Maddy van Lent at Regional Public Health Service Hart voor Brabant, Fleur Groenendijk at Regional Public Health Service Zeeland, Kitty Suijk at Leiden University Medical Centre, Leiden; all the travel nurses and Bert Doornekamp at Ease travel Clinic & Health Support; Astrid Oude Lashof at the Department of Medical Microbiology, Maastricht University Medical Center, Maastricht; Adrie van't Hof at Regional Public Health Zuid Holland Zuid; John van Gulik, Diana Pols, and Angelique Blom at the Regional Public Health Service Rotterdam-Rijnmond; Yvonne Sterken at the Regional Public Health Service Gelderland-Zuid; Yvette Donkers at the Regional Public Health Service Brabant-Zuidoost; Carol Niesen at the Regional Public Health Service Limburg-Noord; Marijke van Cooten, Leanne van der Hoek, Johan Versteegen, and Kees Dirksen at the Regional Public Health Service; Den Haag, Annemarie Siebelink, and Maaike Bosschart at the Regional Public Health Service Gelderland Midden; Greet Boland at Utrecht University Medical Centre, Utrecht; Anne de Vries, and Nicole Leerssen at the Regional Public Health Service Kennemerland; Lieke Winkeler, Marieke Laheij, and Ashis Brahma at the Regional Public Health Service Noord-en Oost-Gelderland. We thank José A. Ferreira from the National Institute for Public Health and the Environment for his valuable comments and help with the data analysis. We thank the laboratory staff and Domenique van Adrichem for their contribution to the laboratory tests at the Department of Medical Microbiology of Leiden University Medical Center.
Funding Information:
This investigator-initiated study received funding from a non-profit independent governmental organisation?namely, the National Institute for Public Health and the Environment (numbers 212-11, 213-11, 214-11, and 215-11). Employees of the National Institute for Public Health and the Environment were involved in the study design, data analysis, interpretation of the results, and writing of the report. GlaxoSmithKline and Merck Sharp & Dohme provided the vaccines used in this study. Neither manufacturer was involved in the study design, data collection, data analysis, interpretation of the results, or writing of the report. We thank all the participating centres for their support; Marita Werner, and Marga Smit at the South Limburg Public Health Service; Mieke Croughs, and Maddy van Lent at Regional Public Health Service Hart voor Brabant, Fleur Groenendijk at Regional Public Health Service Zeeland, Kitty Suijk at Leiden University Medical Centre, Leiden; all the travel nurses and Bert Doornekamp at Ease travel Clinic & Health Support; Astrid Oude Lashof at the Department of Medical Microbiology, Maastricht University Medical Center, Maastricht; Adrie van't Hof at Regional Public Health Zuid Holland Zuid; John van Gulik, Diana Pols, and Angelique Blom at the Regional Public Health Service Rotterdam-Rijnmond; Yvonne Sterken at the Regional Public Health Service Gelderland-Zuid; Yvette Donkers at the Regional Public Health Service Brabant-Zuidoost; Carol Niesen at the Regional Public Health Service Limburg-Noord; Marijke van Cooten, Leanne van der Hoek, Johan Versteegen, and Kees Dirksen at the Regional Public Health Service; Den Haag, Annemarie Siebelink, and Maaike Bosschart at the Regional Public Health Service Gelderland Midden; Greet Boland at Utrecht University Medical Centre, Utrecht; Anne de Vries, and Nicole Leerssen at the Regional Public Health Service Kennemerland; Lieke Winkeler, Marieke Laheij, and Ashis Brahma at the Regional Public Health Service Noord-en Oost-Gelderland. We thank Jos? A. Ferreira from the National Institute for Public Health and the Environment for his valuable comments and help with the data analysis. We thank the laboratory staff and Domenique van Adrichem for their contribution to the laboratory tests at the Department of Medical Microbiology of Leiden University Medical Center.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/1
Y1 - 2020/1
N2 - Background Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunityMethods Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre = 10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40).Findings The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57.9-75.1 in the control group, 94 (80%) of the 118 (71.346.5) in the Twinrix group, 95 (83%) of 114 (75.2-89.7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79.9-92.4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21.6% [95% CI 10.4-32.7], p=0.0204 [Bonferroni corrected p value]) and the Fendrix group (26.3%[15.4-37.3], p=0.0006), but not the Twinrix group (25.0% [13.0-37-0]; 1:0 .0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine.Interpretation Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders. Copyright (C) 2019 Elsevier Ltd. All right reserved.
AB - Background Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunityMethods Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre = 10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40).Findings The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57.9-75.1 in the control group, 94 (80%) of the 118 (71.346.5) in the Twinrix group, 95 (83%) of 114 (75.2-89.7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79.9-92.4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21.6% [95% CI 10.4-32.7], p=0.0204 [Bonferroni corrected p value]) and the Fendrix group (26.3%[15.4-37.3], p=0.0006), but not the Twinrix group (25.0% [13.0-37-0]; 1:0 .0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine.Interpretation Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders. Copyright (C) 2019 Elsevier Ltd. All right reserved.
KW - VACCINE
KW - IMMUNOGENICITY
KW - IMMUNIZATION
KW - EFFICACY
U2 - 10.1016/S1473-3099(19)30417-7
DO - 10.1016/S1473-3099(19)30417-7
M3 - Article
SN - 1473-3099
VL - 20
SP - 92
EP - 101
JO - Lancet Infectious Diseases
JF - Lancet Infectious Diseases
IS - 1
ER -