Time to change dosing of inactivated quadrivalent influenza vaccine in young children: Evidence from a phase III, randomized, controlled trial

Varsha K. Jain, Joseph B. Domachowske, Long Wang, Opokua Ofori-Anyinam, Miguel A. Rodríguez-Weber, Michael L. Leonardi, Nicola P. Klein, Gary Schlichter, Robert Jeanfreau, Byron L. Haney, Laurence Chu, Jo Ann S. Harris, Kwabena O. Sarpong, Amanda C. Micucio, Jyoti Soni, Vijayalakshmi Chandrasekaran, Ping Li, Bruce L. Innis

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background. Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. Methods. 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). Results. 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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalJournal of the Pediatric Infectious Diseases Society
Issue number1
StatePublished - 2017
Externally publishedYes


  • Children
  • Double-dose
  • Inactivated quadrivalent influenza vaccine

ASJC Scopus subject areas

  • General Medicine


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