Airey Jolanta, Albano Frank R, Sawlwin Daphne C, Jones Alison Graves, Formica Neil, Matassa Vince, Leong Jane
Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia.
Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia.
Vaccine. 2017 May 9;35(20):2745-2752. doi: 10.1016/j.vaccine.2017.03.028. Epub 2017 Apr 5.
Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5-17years.
Participants (N=2278) were randomized 3:1 and stratified by age (5-8years; 9-17years) to receive IIV4 (n=1709) or comparator IIV4 (n=569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI]≤1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI≤10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively.
IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were -3.1 (-8.0, 1.8), 0.4 (-4.5, 5.3), -3.4 (-8.3, 1.5), and -2.0 (-6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported.
IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5-17years. Increased levels of virus splitting agent seem to have reduced fever rates observed in children with Seqirus IIV3, particularly those aged 5-8years.
Seqirus Pty Ltd; Clinicaltrials.gov identifier: NCT02545543.
Seqirus 2010南半球裂解病毒三价灭活流感疫苗（IIV3）与儿童发热反应增加有关。体外研究得出结论，裂解剂浓度增加会降低残留脂质，并减弱与发热相关的促炎细胞因子信号。我们评估了一种四价灭活流感疫苗（IIV4；使用更高浓度的裂解剂生产）与一种美国许可的对照IIV4在5至17岁健康儿童中的免疫原性和安全性。
参与者（N = 2278）按3:1随机分组，并按年龄（5至8岁；9至17岁）分层，以接受IIV4（n = 1709）或对照IIV4（n = 569）。主要目标是通过血凝抑制（HI）几何平均滴度（GMT）比值（双侧95%置信区间[CI]的上限≤1.5）和所有四种疫苗毒株的血清转化率差异（双侧95% CI的上限≤10%）来证明IIV4相对于对照IIV4的非劣效性。在基线和接种疫苗后28天评估HI抗体滴度。分别在接种疫苗后的每个7天和28天期间评估主动和被动不良事件。
IIV4符合非劣效性的免疫原性标准。A/H1N1、A/H3N2、B/ Yamagata和B/Victoria毒株的调整后GMT比值（对照IIV4/IIV4）分别为1.01（95% CI；0.93，1.09）、1.05（0.96，1.15）、0.89（0.81，0.98）和0.92（0.83，1.02）。血清转化率差异（对照IIV4减去IIV4）的相应值（95% CI）分别为-3.1（-8.0，1.8）、0.4（-4.5，5.3）、-3.4（-8.3，1.5）和-2.0（-6.9，2.9）。IIV4的发热率在数值上更高，但与对照IIV4相比无统计学差异。未报告新的安全信号。
IIV4在5至17岁儿童中表现出与对照IIV4在免疫学上的非劣效性，且具有临床可接受的安全性。病毒裂解剂水平的提高似乎降低了Seqirus IIV3儿童中观察到的发热率，特别是5至8岁的儿童中。
Seqirus Pty Ltd；Clinicaltrials.gov标识符：NCT02545543。
