Article

A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children

Department of Paediatrics, University of Oxford, Oxford, UK.
Health technology assessment (Winchester, England) 12/2011; 15(45):v-vi, xi-xiii, 1-128. DOI: 10.3310/hta15450
Source: PubMed

ABSTRACT Pandemic influenza A H1N1 infections occurred worldwide from 2009. Children were particularly vulnerable. Novel vaccines were used during the pandemic.
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.
Multicentre, open-label, follow-on from randomised, head-to-head trial.
Five UK sites (Southampton, Oxford, Bristol, London and Exeter).
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.
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.
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.
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.
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.
ClinicalTrials.gov NCT01239537.
The National Institute for Health Research Health Technology Assessment programme.

Download full-text

Full-text

Available from: Adam Finn, Dec 22, 2013
0 Followers
 · 
125 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza A infection has been described as a major viral cause of infection-induced rhabdomyolysis, but to date, only one reported case was described as having been induced by influenza vaccine. We describe a case of a man who had been using statins and developed rhabdomyolysis the day after influenza A H1N1 vaccination. A 58-year-old man was admitted at the emergency room complaining of impaired gait. The patient reported receiving influenza A H1N1 vaccine 5 days prior to the admission, with symptoms beginning the day after the inoculation. He reported ascending weakness, intense myalgia in the lower back, upper and lower limbs. The admission laboratory tests showed serum creatine phosphokinase: 7600 IU/L, creatinine: 3.0 mg/dL, urea: 185 mg/dL, aspartate aminotransferase: 592 IU/L, alanine aminotransferase: 630 IU/L, potassium: 5.4 mEq/L, lactate dehydrogenase: 2828 IU/L. Despite intravenous fluid therapy, the patient still persisted with oliguria and urinary output of 0.17 ml/kg/h. Hemodialysis was initiated and renal function recovery was observed after two weeks. The patient was hemodynamically stable and asymptomatic at hospital discharge. This is a rare side effect of influenza A H1N1 vaccine. Physicians should advise patients to seek medical care when muscle symptoms are present and consider the possibility of rhabdomyolysis due to vaccination. Trials are required to better define the incidence of this important side effect.
    Travel Medicine and Infectious Disease 12/2012; 11(2). DOI:10.1016/j.tmaid.2012.11.004 · 1.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. We report a follow up clinical and serological investigation of 274 children receiving seasonal influenza vaccine (TIV) one year after receipt of either AS03B-adjuvanted subunit or whole virus monovalent A(H1N1)pdm09 vaccine and describe the antibody responses to the H3N2 A/Perth/16/2009 and B/Brisbane/60/2008 components of TIV. Method and Findings. Vaccine responses were analysed using Haemagglutination Inhibition (HAI) assays. In individuals under 3 years of age, previous receipt of adjuvanted vaccine resulted in higher HAI antibody responses to H3N2 and B strains compared to non-adjuvanted vaccine (fold change 16.8 vs 4.3 for H3N2 and 7.0 vs 1.6 for B). In older children, responses to the H3 and B components of TIV were similar between vaccine groups. Sera taken pre- and post pandemic vaccine were also analysed by HAI with A/Perth/16/2009 virus. This analysis showed that 11.1% of children receiving the AS03B-adjuvanted vaccine but only 1.4% in the non-adjuvanted group had a 4-fold rise to A/Perth/16/2009. Conculsion. AS03B-adjuvanted A(H1N1)pdm09 influenza vaccine generates a cross-reactive antibody response to H3N2 in children and enhances responses to heterologous subtypes in <3-year-old children one year later.
    Clinical Infectious Diseases 10/2013; 58(2). DOI:10.1093/cid/cit692 · 9.42 Impact Factor