title: Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial.
abstract: Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose.
  We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424).
  Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events.
  Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.
authors.affiliation: GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Varsha K
authors.initials: VK
authors.lastname: Jain
authors.affiliation: SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.affiliation: GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.affiliation: Instituto Nacional de Pediatría de México, Mexico City.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodríguez-Weber
authors.affiliation: Palmetto Pediatrics, Charleston, South Carolina.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Leonardi
authors.affiliation: Kaiser Permanente Vaccine Study Center, Oakland, California.
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.affiliation: Jean Brown Research, Salt Lake City, Utah.
authors.forename: Gary
authors.initials: G
authors.lastname: Schlichter
authors.affiliation: MedPharmics, Metairie, Louisiana.
authors.forename: Robert
authors.initials: R
authors.lastname: Jeanfreau
authors.affiliation: Family Health Care of Ellensburg, Ellensburg and Pacific Northwest University, Yakima, Washington.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Haney
authors.affiliation: Benchmark Research, Austin, Texas.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chu
authors.affiliation: Stormont Vail Health, Topeka, Kansas.
authors.forename: Jo-Ann S
authors.initials: JS
authors.lastname: Harris
authors.affiliation: Sealy Center for Vaccine Development University of Texas Medical Branch, Galveston.
authors.forename: Kwabena O
authors.initials: KO
authors.lastname: Sarpong
authors.affiliation: Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Micucio
authors.affiliation: GlaxoSmithKline Pharmaceuticals Ltd, Bangalore, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Soni
authors.affiliation: GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Chandrasekaran
authors.affiliation: GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000074099:Equivalence Trials as Topic; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D008297:Male
chemical_list: C000618615:Fluzone High-Dose; D007252:Influenza Vaccines
keywords: children; double-dose; inactivated quadrivalent influenza vaccine.