Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study |
| |
| Affiliation: | 1. University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, United States;2. Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia;3. Pharmacovigilance and Risk Management, Seqirus Pty Ltd, Parkville, Victoria, Australia;4. Medical Affairs, Seqirus Pty Ltd, Parkville, Victoria, Australia |
| |
| Abstract: | BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18 years.MethodsParticipants (n = 3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n = 1741), IIV3-YAM (n = 871), or IIV3-VIC (n = 872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI ≤ 10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination.ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were −1.1 (−4.5, 2.3), −1.7 (−5.0, 1.7), −3.2 (IIV3-YAM; −7.4, 0.9), and −1.6 (IIV3-VIC; −5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%).ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225. |
| |
| Keywords: | Immunogenicity Inactivated Influenza vaccine Noninferiority Quadrivalent Safety AE" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" adverse event CI" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" confidence interval DSMB" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" Data and Safety Monitoring Board FAS" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" full analysis set GMFI" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" geometric mean fold increase GMT" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" geometric mean titer HI" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" hemagglutination inhibition IIV3" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" trivalent inactivated influenza vaccine IIV4" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" quadrivalent inactivated influenza vaccine LS" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" least square SAE" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" serious adverse event SCR" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" seroconversion rate SD" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" standard deviation SPR" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" seroprotection rate US" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" United States VIC" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" Victoria YAM" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" Yamagata |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
