title: A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children.
abstract: BACKGROUND
  Pandemic influenza A H1N1 infections occurred worldwide from 2009. Children were particularly vulnerable. Novel vaccines were used during the pandemic.
  
  
  OBJECTIVE
  To assess the persistence of antibody to H1N1 influenza 1 year after children aged 6 months to 12 years had been immunised with two doses of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine; and also to assess the immunogenicity and reactogenicity in this population of a single dose of 2010-11 trivalent seasonal influenza vaccine.
  
  
  METHODS
  Multicentre, open-label, follow-on from randomised, head-to-head trial.
  
  
  METHODS
  Five UK sites (Southampton, Oxford, Bristol, London and Exeter).
  
  
  METHODS
  Children who completed last year's head-to-head randomised study were invited to participate. Children who had subsequently received a further dose of H1N1 vaccine, or who had already received a dose of 2010-11 trivalent seasonal influenza vaccine, were excluded.
  
  
  METHODS
  In the previous study, children were randomised (in a 1 : 1 ratio) to receive two doses, 21 days apart, of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine. In this follow-on study, a blood sample was taken to assess the persistence of antibody 1 year later, followed by administration of one 0.5 ml-dose of trivalent seasonal influenza vaccine. A second blood sample was taken 3 weeks later.
  
  
  METHODS
  Comparison between vaccines of the percentage of participants with a microneutralisation (MN) titre ≥ 1 : 40 and a haemagglutination titre ≥ 1 : 32, 1 year after vaccination. Immunogenicity of the trivalent seasonal influenza vaccine was assessed 3 weeks after vaccination by both the MN and the haemagglutination inhibition (HI) titres. Reactogenicity data were recorded for 7 days after vaccination.
  
  
  RESULTS
  A total of 323 children were enrolled and 318 were included in the analysis of the persistence of antibody. One year after receipt of whole-virion vaccine, the MN titre was ≥ 1 : 40 in 32.4% of those vaccinated when < 3 years old and in 65.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 63.2% and 79.1% of children in the respective age groups. One year after receipt of the adjuvanted vaccine, the MN titre was ≥ 1 : 40 in 100% of those vaccinated when < 3 years old and in 96.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 98.4% and 96.9% of children in the respective age groups. Three hundred and two children were given trivalent seasonal influenza vaccination. Three weeks later, sera were obtained from 282 children; 100% had an MN titre ≥ 1 : 40 and HI titre ≥ 1 : 32. Trivalent seasonal influenza vaccine was well tolerated, although in children < 5 years old, fever ≥ 38 °C was reported in 13.6% of those who had previously received whole-virion vaccine, and in 18.3% of those who had received adjuvanted vaccine.
  
  
  CONCLUSIONS
  Nearly all children who received two doses of AS03B-adjuvanted split-virion pandemic H1N1 influenza vaccine had titres of antibody deemed protective (HI titre ≥ 1 : 32, MN titre ≥ 1 : 40) 1 year later. Children who received two doses of whole-virion vaccine had lower titres, although many were above the putative protective thresholds. One year after either pandemic vaccine, the 2010-11 trivalent seasonal influenza vaccine produced a marked serological response to the H1N1 component of the vaccine and was well tolerated. We propose to investigate whether or not previous receipt of monovalent influenza vaccines affected serological response to the H3N2 and B components of the 2010-11 seasonal influenza vaccine, using stored sera.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01239537.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: de Whalley
authors.forename: W
authors.initials: W
authors.lastname: Walker
authors.forename: M D
authors.initials: MD
authors.lastname: Snape
authors.forename: C
authors.initials: C
authors.lastname: Oeser
authors.forename: M
authors.initials: M
authors.lastname: Casey
authors.forename: P
authors.initials: P
authors.lastname: Moulsdale
authors.forename: C
authors.initials: C
authors.lastname: Harrill
authors.forename: N
authors.initials: N
authors.lastname: Andrews
authors.forename: K
authors.initials: K
authors.lastname: Hoschler
authors.forename: B
authors.initials: B
authors.lastname: Thompson
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Chalk
authors.forename: S
authors.initials: S
authors.lastname: Kerridge
authors.forename: R
authors.initials: R
authors.lastname: Tomlinson
authors.forename: P T
authors.initials: PT
authors.lastname: Heath
authors.forename: A
authors.initials: A
authors.lastname: Finn
authors.forename: S
authors.initials: S
authors.lastname: Faust
authors.forename: E
authors.initials: E
authors.lastname: Miller
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D016001:Confidence Intervals; D004196:Disease Outbreaks / Q000517:prevention & control*; D064420:Drug-Related Side Effects and Adverse Reactions; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000517:prevention & control*; D006113:United Kingdom
chemical_list: D007252:Influenza Vaccines