Elsevier

Vaccine

Volume 37, Issue 2, 7 January 2019, Pages 343-351
Vaccine

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

https://doi.org/10.1016/j.vaccine.2018.07.036Get rights and content
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Funding

Seqirus Pty Ltd; ClinicalTrials.gov identifier: NCT02914275.

Keywords

Immunogenicity
Inactivated influenza vaccine
Paediatrics
Quadrivalent influenza vaccine
Safety

Abbreviations

AE
adverse event
C-IIV4
comparator quadrivalent inactivated influenza vaccine
CBER
Center for Biologics Evaluation and Research
CI
confidence interval
DSMB
Data and Safety Monitoring Board
eDiary
electronic diary
FAS
full analysis set
FDA
Food and Drug Administration
GMFI
geometric mean fold increase
GMT
geometric mean titer
HA
hemagglutinin
HI
hemagglutination inhibition
S-IIV3
Seqirus trivalent inactivated influenza vaccine
S-IIV4
Seqirus quadrivalent inactivated influenza vaccine
SAE
serious adverse event
SCR
seroconversion rate
SD
standard deviation
US
United States
VIC
Victoria
YAM
Yamagata

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