title: Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months.
abstract: OBJECTIVE
  We assessed whether 2 full versus 2 half-doses of trivalent inactivated influenza vaccine (TIV) could improve immunogenicity without increasing reactogenicity in infants (aged 6-11 months) and toddlers (aged 12-23 months).
  
  
  METHODS
  Previously unimmunized infants and toddlers were separately randomly assigned to receive 2 full (0.5-mL) or 2 half (0.25-mL) doses of 2008-2009 split TIV. Sera were collected at enrollment and at 27 to 45 days after the second injection. Parents recorded adverse events after each injection. The primary immunogenicity outcome was superiority (1-sided, α = 0.025) of the full versus the half-dose based on a >10% increase in rates of seroprotection (hemagglutination inhibition titer of ≥40). The primary reactogenicity outcome was fever of ≥38°C within 3 days of either injection.
  
  
  RESULTS
  In per-protocol analyses, 252 participants (full dose: n = 124; half-dose: n = 128) were included. In toddlers, postimmunization seroprotection rates exceeded 85% for all 3 vaccine components without significant difference by dose. In infants, the full dose induced higher responses for all 3 vaccine components, meeting the 10% test of superiority for the H3N2 (75.4% vs 47.6%; Δ = 27.8% [95% confidence interval (CI): 11.2-44.5]; P = .02) and B/Yamagata (70.2% vs 41.3%; Δ = 28.9% [95% CI: 11.9-45.9]; P = .02) components but not H1N1 (71.9% vs 54.0%; Δ = 18.0% [95% CI: 1.0-34.9]; P = .2). Rates of fever were not increased among full- versus half-dose recipients in either age group (5.6% vs 12.7% combined).
  
  
  CONCLUSIONS
  Administration of 2 full TIV doses may improve immunogenicity without increasing reactogenicity in infants. Current TIV dosing recommendations for young children warrant additional evaluation.
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada. danuta.skowronski@bccdc.ca
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.forename: Travis S
authors.initials: TS
authors.lastname: Hottes
authors.forename: Mei
authors.initials: M
authors.lastname: Chong
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.forename: David W
authors.initials: DW
authors.lastname: Scheifele
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Naveed Z
authors.initials: NZ
authors.lastname: Janjua
authors.forename: Tracy
authors.initials: T
authors.lastname: Chan
authors.forename: Suzana
authors.initials: S
authors.lastname: Sabaiduc
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
mesh_terms: D000367:Age Factors; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007125:Immunogenetics / Q000379:methods; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000097:blood; D007251:Influenza, Human / Q000097:blood / Q000517:prevention & control*; D008297:Male; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000097:blood
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated