title: Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study.
abstract: BACKGROUND
  Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making.
  
  
  METHODS
  Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621.
  
  
  RESULTS
  Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5°C) was more common in two-dose compared to one dose recipients (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p<0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident.
  
  
  CONCLUSIONS
  Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero-protected for A/H1N1 after receipt of the 2010-11 TIV.
authors.affiliation: Canadian Center for Vaccinology, Dalhousie University and IWK Health Centre Halifax, Halifax, Nova Scotia, B3K 6R8, Canada. Joanne.Langley@dal.ca
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.forename: David W
authors.initials: DW
authors.lastname: Scheifele
authors.forename: Caroline
authors.initials: C
authors.lastname: Quach
authors.forename: Otto G
authors.initials: OG
authors.lastname: Vanderkooi
authors.forename: Brian
authors.initials: B
authors.lastname: Ward
authors.forename: Shelly
authors.initials: S
authors.lastname: McNeil
authors.forename: Simon
authors.initials: S
authors.lastname: Dobson
authors.forename: James D
authors.initials: JD
authors.lastname: Kellner
authors.forename: Susan
authors.initials: S
authors.lastname: Kuhn
authors.forename: Tobias
authors.initials: T
authors.lastname: Kollman
authors.forename: Donna
authors.initials: D
authors.lastname: MacKinnon-Cameron
authors.forename: Bruce
authors.initials: B
authors.lastname: Smith
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D002170:Canada; D002675:Child, Preschool; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007407:Interviews as Topic; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D011446:Prospective Studies; D013185:Squalene / Q000008:administration & dosage; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D015164:Vaccines, Inactivated; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol