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Clinical Trial
. 2017 Mar 1;6(1):9-19.
doi: 10.1093/jpids/piw068.

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

Varsha K Jain  1 , Joseph B Domachowske  2 , Long Wang  1 , Opokua Ofori-Anyinam  3 , Miguel A Rodríguez-Weber  4 , Michael L Leonardi  5 , Nicola P Klein  6 , Gary Schlichter  7 , Robert Jeanfreau  8 , Byron L Haney  9 , Laurence Chu  10 , Jo-Ann S Harris  11 , Kwabena O Sarpong  12 , Amanda C Micucio  13 , Jyoti Soni  14 , Vijayalakshmi Chandrasekaran  1 , Ping Li  1 , Bruce L Innis  1
Affiliations
Clinical Trial

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

Varsha K Jain et al. J Pediatric Infect Dis Soc. .

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.

Keywords: children; double-dose; inactivated quadrivalent influenza vaccine..

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Figures

Figure 1.
Figure 1.
Participant disposition.
Figure 2.
Figure 2.
Geometric mean titer for all vaccine strains in all children 6–35 months of age regardless of priming status and in each subgroup prevaccination and 28 days after completion of vaccination series (per-protocol cohort). CI, confidence interval; IIV4, inactivated quadrivalent influenza vaccine.
Figure 3.
Figure 3.
Noninferiority of the double-dose versus the standard-dose in all children 6–35 months of age regardless of priming status: geometric mean titer (GMT) ratio and difference in seroconversion rate (SCR) at 28 days after completion of vaccination series (per-protocol cohort). CI, confidence interval; IIV4, inactivated quadrivalent influenza vaccine.
Figure 4.
Figure 4.
Comparison of immunogenicity of the double-dose versus the standard-dose in all children 6–35 months of age regardless of priming status and in each subgroup: geometric mean titer (GMT) ratio and difference in seroconversion rate (SCR) at 28 days after completion of vaccination series (per-protocol cohort). CI, confidence interval; IIV4, inactivated quadrivalent influenza vaccine.
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References

    1. O’Brien MA, Uyeki TM, Shay DK, et al. Incidence of outpatient visits and hospitalizations related to influenza in infants and young children. Pediatrics 2004; 113:585–93. - PubMed
    1. Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000; 342:232–9. - PubMed
    1. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 2007; 25:5086–96. - PubMed
    1. Bourgeois FT, Valim C, Wei JC, et al. Influenza and other respiratory virus-related emergency department visits among young children. Pediatrics 2006; 118:e1–8. - PubMed
    1. Centers for Disease Control and Prevention (CDC). Influenza-associated pediatric deaths–United States, September 2010-August 2011. MMWR Morb Mortal Wkly Rep 2011; 60:1233–8. - PubMed