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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

tetano

Editor, Senior Moderator
Vaccine. 2018 Jul 26. pii: S0264-410X(18)31005-3. doi: 10.1016/j.vaccine.2018.07.036. [Epub ahead of print]
[h=1]Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study.[/h] Statler VA[SUP]1[/SUP], Albano FR[SUP]2[/SUP], Airey J[SUP]3[/SUP], Sawlwin DC[SUP]4[/SUP], Graves Jones A[SUP]4[/SUP], Matassa V[SUP]3[/SUP], Heijnen E[SUP]5[/SUP], Edelman J[SUP]6[/SUP], Marshall GS[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSION:[/h] 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.
[h=4]FUNDING:[/h] Seqirus Pty Ltd; ClinicalTrials.gov identifier:NCT02914275.
Copyright ? 2018. Published by Elsevier Ltd.


[h=4]KEYWORDS:[/h] Immunogenicity; Inactivated influenza vaccine; Paediatrics; Quadrivalent influenza vaccine; Safety

PMID: 30057283 DOI: 10.1016/j.vaccine.2018.07.036
 
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