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Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age

Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age
Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age
Background: 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.

Objectives:

Immunogenicity
•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?

Reactogenicity
•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?

Methods: 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.

Results: 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%).

Conclusion: 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.
1366-5278
1-130
Waddington, C.S.
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Andrews, N.
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Hoschler, K.
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Walker, W.T.
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Oeser, C.
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Reiner, A.
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John, T.
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Wilkinson, Suzanne
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Casey, M.
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Eccleston, P.E.
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Allen, R.J.
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Okike, I.
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Ladhani, S.
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Sheasby, E.
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Waight, P.
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Collinson, A.C.
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Heath, P.T,
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Finn, A.
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Faust, S.N.
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Snape, M.D.
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Miller, E.
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Pollard, A.J.
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Waddington, C.S.
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Andrews, N.
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Hoschler, K.
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Walker, W.T.
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Oeser, C.
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Reiner, A.
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John, T.
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Wilkinson, Suzanne
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Casey, M.
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Eccleston, P.E.
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Allen, R.J.
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Okike, I.
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Ladhani, S.
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Sheasby, E.
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Waight, P.
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Collinson, A.C.
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Heath, P.T,
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Finn, A.
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Faust, S.N.
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Snape, M.D.
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Miller, E.
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Pollard, A.J.
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Waddington, C.S., Andrews, N., Hoschler, K., Walker, W.T., Oeser, C., Reiner, A., John, T., Wilkinson, Suzanne, Casey, M., Eccleston, P.E., Allen, R.J., Okike, I., Ladhani, S., Sheasby, E., Waight, P., Collinson, A.C., Heath, P.T,, Finn, A., Faust, S.N., Snape, M.D., Miller, E. and Pollard, A.J. (2010) Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age. Health Technology Assessment, 14 (46), 1-130. (PMID:20923610)

Record type: Article

Abstract

Background: 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.

Objectives:

Immunogenicity
•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?

Reactogenicity
•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?

Methods: 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.

Results: 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%).

Conclusion: 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.

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More information

Published date: October 2010

Identifiers

Local EPrints ID: 175589
URI: http://eprints.soton.ac.uk/id/eprint/175589
ISSN: 1366-5278
PURE UUID: 4b8f5352-2d21-46a6-ab24-f128d5075357
ORCID for S.N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 24 Feb 2011 14:59
Last modified: 23 Jul 2022 01:56

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Contributors

Author: C.S. Waddington
Author: N. Andrews
Author: K. Hoschler
Author: W.T. Walker
Author: C. Oeser
Author: A. Reiner
Author: T. John
Author: Suzanne Wilkinson
Author: M. Casey
Author: P.E. Eccleston
Author: R.J. Allen
Author: I. Okike
Author: S. Ladhani
Author: E. Sheasby
Author: P. Waight
Author: A.C. Collinson
Author: P.T, Heath
Author: A. Finn
Author: S.N. Faust ORCID iD
Author: M.D. Snape
Author: E. Miller
Author: A.J. Pollard

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