Executive summary of HTA journal title
Health Technol Assess 2010;14(46):1–130
Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03B/oil-in-water emulsion-adjuvanted (AS03B) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age
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CS Waddington,1* N Andrews,2 K Hoschler,2 WT Walker,3 C Oeser,4 A Reiner,1 T John,1 S Wilkins,5 M Casey,3 PE Eccleston,6 RJ Allen,6 I Okike,4 S Ladhani,2,4 E Sheasby,2 P Waight,2 AC Collinson,5 PT Heath,4 A Finn,6 SN Faust,3 MD Snape,1 E Miller2 and AJ Pollard1
1Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
2Centre for Infections, Health Protection Agency, London, UK
3University of Southampton Wellcome Trust Clinical Research Facility and Division of Infection, Inflammation & Immunity, Southampton, UK
4St George’s Vaccine Institute, London, UK
5Royal Devon & Exeter NHS Foundation Trust, Exeter, UK
6Bristol Children’s Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK
Children are a priority for vaccination in an influenza pandemic, but safety and immunogenicity data for new-generation adjuvanted and whole-virion vaccines are limited.
- How does the percentage of children aged 6 months to 12 years of age with a fourfold rise in microneutralisation titres between the prevaccination sample and the sample taken 3 weeks after completion of a two-dose course of the non-adjuvanted, whole-virion vaccine and the AS03B-adjuvanted split-virion vaccine compare?
- How does the percentage of children aged 6 months to 12 years of age with haemagglutination inhibition titres of ≥ 1 : 32 3 weeks after completion of a two-dose course of the non-adjuvanted, whole-virion vaccine and the AS03B-adjuvanted split-virion vaccine compare?
- How does the percentage of children aged 6 months to 12 years of age with a fourfold rise in haemagglutination inhibition titres between the prevaccination sample and the sample taken 3 weeks after completion of a two-dose course of the non-adjuvanted, whole-virion vaccine and the AS03B-adjuvanted split-virion vaccine compare?
- What is the geometric mean fold rise in haemagglutination inhibition titres from baseline to 3 weeks after two doses of the non-adjuvanted, whole-virion vaccine and the AS03B-adjuvanted split-virion vaccine?
- What is the geometric mean haemagglutination inhibition titre 3 weeks after two doses of the non-adjuvanted, whole-virion vaccine and the AS03B-adjuvanted split-virion vaccine?
- How does the percentage of children aged 6 months to 12 years of age experiencing fever and local reactions within the 7 days following each dose of the non-adjuvanted, whole-virion and the AS03B-adjuvanted split-virion vaccines compare?
- What percentage of children aged 6 months to 12 years of age experience non-febrile systemic reactions within the 7 days following each dose of the non-adjuvanted, whole-virion and the AS03B-adjuvanted split-virion vaccine?
The safety, reactogenicity and immunogenicity of a tocopherol/oil-in-water emulsion-adjuvanted (AS03B) egg culture-derived split-virion H1N1 vaccine and a non-adjuvanted cell culture-derived whole-virion vaccine, given as a two-dose schedule, 21 days apart, were compared in a randomised, open-label trial of children aged 6 months to 12 years of age. Local reactions and systemic symptoms were collected for 1 week post immunisation, and serum was collected at baseline and after the second dose.
Among 937 children receiving vaccine, per-protocol seroconversion rates were higher after the AS03B-adjuvanted vaccine than after the whole-virion vaccine (98.2% vs 80.1% in children < 3 years, 99.1% vs 95.9% among those aged 3–12 years), as were severe local reactions (3.6% vs 0.0% in those under 5 years, and 7.8% vs 1.1% in those aged 5–12 years), irritability in children < 5 years (46.7% vs 32.0%), and muscle pain in older children (28.9% vs 13.2%). The second dose of the adjuvanted vaccine was more reactogenic than the first especially for fever > 38.0°C in those under 5 years of age (8.9% vs 22.4%).
In this first direct comparison of an AS03B-adjuvanted split-virion vaccine versus whole-virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine – while reactogenic – was more immunogenic, especially in younger children, indicating the potential for improved immunogenicity of influenza vaccines in this age group.
This trial was registered as ISRCTN89141709.
Waddington CS, Andrews N, Hoschler K, Walker WT, Oeser C, Reiner A, et al. Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03B/oil-in-water emulsion-adjuvanted (AS03B) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age. Health Technol Assess 2010;14(46):1–130.
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