Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial

Abstract

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.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2017–18 Influenza Season

“…In a randomized trial comparing immunogenicity and safety of 0.5 mL FluLaval Quadrivalent with 0.25 mL Fluzone Quadrivalent, safety and reactogenicity were similar between the two vaccines. In a post-hoc analysis, superior immunogenicity was noted for the B components of FluLaval Quadrivalent among infants aged 6 through 17 months and for unprimed children (those who had not previously received at least 2 doses of influenza vaccine) aged 6 through 35 months ( 30 ).…”

Immunization update 2019

“…24 A post hoc analysis showed superior immunogenicity for the B strain components of FluLaval Quadrivalent among children aged 6 through 17 months and those who had not previously received at least two doses of influenza vaccine. 24 The authors concluded that the double dose may improve protection against influenza B in some young children.…”

“…23 FluLaval demonstrated safety and efficacy of the double dose for children younger than age 3 in a Phase III, randomized, observer-blinded, controlled trial. 24 The study assessed immunogenicity (geometric mean titers and seroconversion rate) in the per-protocol cohort (n = 2,041) and safety (adverse event reports) in the intent-to-treat cohort (n = 2,424). 24 Safety and reactogenicity were similar for a 0.5-mL dose of FluLaval Quadrivalent and a 0.25-mL dose of Fluzone Quadrivalent.…”

“…24 The study assessed immunogenicity (geometric mean titers and seroconversion rate) in the per-protocol cohort (n = 2,041) and safety (adverse event reports) in the intent-to-treat cohort (n = 2,424). 24 Safety and reactogenicity were similar for a 0.5-mL dose of FluLaval Quadrivalent and a 0.25-mL dose of Fluzone Quadrivalent. 24 A post hoc analysis showed superior immunogenicity for the B strain components of FluLaval Quadrivalent among children aged 6 through 17 months and those who had not previously received at least two doses of influenza vaccine.…”

Prevention and Control of Seasonal Influenza With Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2017–18 Influenza Season

“…In a randomized trial comparing immunogenicity and safety of 0.5 mL FluLaval Quadrivalent with 0.25 mL Fluzone Quadrivalent, safety and reactogenicity were similar between the two vaccines. In a post‐hoc analysis, superior immunogenicity was noted for the B components of FluLaval Quadrivalent among infants aged 6 through 17 months and for unprimed children (those who had not previously received at least 2 doses of influenza vaccine) aged 6 through 35 months .…”