In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38. °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.
Bibliographical noteFunding Information:
Conflict of interests: Vaccines were manufactured by GlaxoSmithKline vaccines and Baxter, both of whom donated the vaccine but had no role in study planning or conduct. AJP, AF, PTH, SNF, ACC act as chief or principal investigators for clinical trials conducted on behalf of their respective NHS Trusts and/or Universities sponsored by vaccine manufacturers but receive no personal payments from them. KH has been investigator of clinical trials sponsored by vaccine manufacturers but received no personal payments from them. AJP, AF, PTH and SNF have participated in advisory boards for vaccine manufacturers but receive no personal payments for this work. MDS, PTH, KH and AF have received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities, or to independent charities. Funding: This work was supported by the NIHR Health Technology Assessment Programme ; Oxford comprehensive Biomedical Research Centre (OxBRC) and the Thames Valley , Hampshire and Isle of Wight , Western and South London Comprehensive Local Research Networks . None of the funders had a role in study design, data collection, analysis, interpretation or writing the paper. This study was adopted by the NIHR Medicines for Children Research Network and supported by their South West and London Local Research Networks. Ethical approval: Ethical approval was obtained from Oxfordshire Research Ethics Committee A (No: 09/H0604/107), the UK Medicines and Healthcare Products Regulatory Agency (EUDRACT 2009-014719-11), and local NHS organisations. Parents or guardians gave written informed consent; children aged 7 and over gave verbal consent. Contributors: AJP, EM, MDS, SNF, AF, PTH, ACC, NA, KH, and CW designed the original study. AJP was chief investigator. MDS, SNF, AF, PTH, and ACC were local principal investigators. NA was responsible for statistical analysis, KH for laboratory analysis and PW for central data management, all with oversight and guidance by EM (lead investigator). AR was Project Manager for the trial. SK was quality manager for the trial. LS contributed to study management and quality assurance. RA contributed to project management at the Bristol site. CW, WTW, CO, TJ, SW, MC, RA, IO, SL, MF, JC, NF, LM, ACC, PTH, AF, SNF, MDS, and AJP enrolled patients and/or contributed to data collection for the original study. NA and EM drafted the paper and AJP, MDS, AF, PTH, SNF, ACC and PW provided critical input to the draft. All authors reviewed the final draft and agree with its contents.
Copyright 2012 Elsevier B.V., All rights reserved.
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