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Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: A phase 3, randomized, noninferiority study

Statler, Victoria A., Albano, Frank R., Airey, Jolanta, Sawlwin, Daphne C., Graves Jones, Alison, Matassa, Vince, Heijnen, Esther, Edelman, Jonathan, Marshall, Gary S.
Vaccine 2019 v.37 no.2 pp. 343-351
children, detergents, fever, geometry, hemagglutination, immunogenicity, influenza, influenza vaccines, lipid content, seizures, seroconversion, United States
In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad™/Afluria Tetra™), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete.Children aged 6–59 months were randomized 3:1 and stratified by age (6–35 months/36–59 months) to receive S-IIV4 (n = 1684) or a United States (US)-licensed comparator IIV4 (C-IIV4; Fluzone® Quadrivalent; n = 563) during the Northern Hemisphere 2016–2017 influenza season. The primary objective was to demonstrate noninferior immunogenicity of S-IIV4 versus C-IIV4. Immunogenicity was assessed by hemagglutination inhibition (baseline, 28 days postvaccination). Solicited, unsolicited, and serious adverse events were assessed for 7, 28, and 180 days postvaccination, respectively.S-IIV4 met the immunogenicity criteria for noninferiority. Adjusted geometric mean titer ratios (C-IIV4/S-IIV4) for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 0.79 (95% CI: 0.72, 0.88), 1.27 (1.15, 1.42), 1.12 (1.01, 1.24), and 0.97 (0.86, 1.09), respectively. Corresponding values for differences in seroconversion rates (C-IIV4 minus S-IIV4) were −10.3 (−15.4, −5.1), 2.6 (−2.5, 7.8), 3.1 (−2.1, 8.2), and 0.9 (−4.2, 6.1). Solicited, unsolicited, and serious adverse events were similar between vaccines in both age cohorts, apart from fever. Fever rates were lower with S-IIV4 (5.8%) than C-IIV4 (8.4%), with no febrile convulsions reported with either vaccine during the 7 days postvaccination.S-IIV4, manufactured with a higher detergent concentration, demonstrated noninferior immunogenicity to the US-licensed C-IIV4, with similar postvaccination safety and tolerability, in children aged 6–59 months. This completes the program demonstrating the immunogenicity and safety of S-IIV4 in participants aged 6 months and older.Seqirus Pty Ltd; identifier:NCT02914275.