title: A randomized controlled study to evaluate the immunogenicity of a trivalent inactivated seasonal influenza vaccine at two dosages in children 6 to 35 months of age.
abstract: The trivalent inactivated influenza vaccine Fluarix™ is licensed in the US for adults and children from 3 years old. This randomized observer-blind study (NCT00764790) evaluated Fluarix™ at two doses; 0.25 ml (Flu-25) and 0.5 ml (Flu-50) in children aged 6-35 months. The primary objective was to demonstrate immunogenic non-inferiority vs. a control vaccine (Fluzone®; 0.25 ml). Children received Flu-25 (n = 1107), Flu-50 (n = 1106) or control vaccine (n = 1104) at Day 0 and for un-primed children, also on Day 28. Serum hemagglutination-inhibition titers were determined pre-vaccination and at Day 28 (primed) or Day 56 (un-primed). Non-inferiority was assessed by post-vaccination geometric mean titer (GMT) ratio, (upper 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper 95% CI ≤ 10%). Reactogenicity/safety was monitored. The immune response to Flu-50 met all regulatory criteria. Indicated by adjusted GMT ratios [with 95% CI], the criteria for non-inferiority of Flu-50 vs. control vaccine were reached for the B/Florida strain (1.13 [1.01-1.25]) but not for the A/Brisbane/H1N1 (1.74 [1.54-1.98]) or A/Uruguay/H3N2 (1.72 [1.57-1.89]) strains. In children aged 18-35 months similar immune responses were observed for Flu-50 and the control vaccine. Flu-50 induced a higher response than Flu-25 for all strains. Temperature (≥ 37.5°C) was reported in 6.2%, 6.4%, and 6.6% of the Flu-25, Flu-50, and control group, respectively. Reactogenicity/safety endpoints were within the same range for all vaccines. In children aged 6-35 months, immune responses with Flu-50 fulfilled regulatory criteria but did not meet the pre-defined criteria for non-inferiority vs. control. This appeared to be due to differences in immunogenicity in children aged<18 months.
authors.affiliation: Universidad Nacional Autonoma de Mexico; Mexico City, Mexico.
authors.forename: Noris
authors.initials: N
authors.lastname: Pavia-Ruz
authors.forename: Miguel
authors.initials: M
authors.lastname: Angel Rodriguez Weber
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: E Anthony S
authors.initials: EA
authors.lastname: Nelson
authors.forename: Angkool
authors.initials: A
authors.lastname: Kerdpanich
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.forename: Peter
authors.initials: P
authors.lastname: Silas
authors.forename: Paul
authors.initials: P
authors.lastname: Qaqundah
authors.forename: Mark
authors.initials: M
authors.lastname: Blatter
authors.forename: Robert
authors.initials: R
authors.lastname: Jeanfreau
authors.forename: Paul
authors.initials: P
authors.lastname: Lei
authors.forename: Varsha
authors.initials: V
authors.lastname: Jain
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Idrissi
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Bruce
authors.initials: B
authors.lastname: Innis
authors.forename: Mathieu
authors.initials: M
authors.lastname: Peeters
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Devaster
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C510903:fluarix
keywords: children; immunogenicity; influenza; trivalent inactivated; vaccine