Schuster Jennifer E, Hamdan Lubna, Dulek Daniel E, Kitko Carrie L, Batarseh Einas, Haddadin Zaid, Stewart Laura S, Stahl Anna, Potter Molly, Rahman Herdi, Kalams Spyros A, Bocchini Claire E, Moulton Elizabeth A, Coffin Susan E, Ardura Monica I, Wattier Rachel L, Maron Gabriela, Grimley Michael, Paulsen Grant, Harrison Christopher J, Freedman Jason L, Carpenter Paul A, Englund Janet A, Munoz Flor M, Danziger-Isakov Lara, Spieker Andrew J, Halasa Natasha B
Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Clin Infect Dis. 2024 Jan 25;78(1):217-226. doi: 10.1093/cid/ciad534.
Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown.
This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively.
During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]).
Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season.
NCT02860039.
我们之前的研究表明，在儿科异基因造血细胞移植（HCT）受者中，与标准剂量四价流感疫苗（SD-QIV）的两剂方案相比，高剂量三价流感疫苗（HD-TIV）的两剂方案具有更高的免疫原性。然而，免疫原性的持久性以及HCT后免疫接种时间作为效应修饰因子的作用尚不清楚。
本II期、多中心、双盲、随机对照试验在3-17岁、异基因HCT后3-35个月的儿童中比较了HD-TIV和SD-QIV，每种制剂均接种两次，间隔28-42天。在基线、每次接种后28-42天以及第二次接种后138-222天测量血凝抑制（HAI）滴度。使用线性混合效应模型，我们估计了针对流感抗原的调整几何平均HAI滴度比值（aGMR：HD-TIV/SD-QIV）。早期和晚期分别定义为HCT后3-5个月和6-35个月。
在3个流感季节（2016-2019年）期间，170名参与者被随机分配接受HD-TIV（n = 85）或SD-QIV（n = 85）。两种疫苗制剂的HAI滴度均维持在显著高于基线的水平，尽管在研究期间HD-TIV相对于SD-QIV的相对免疫原性益处有所减弱。与HCT后早期相比，HCT后晚期接种的两剂HD-TIV系列与更高的几何平均滴度相关（晚期组：A/H1N1 aGMR = 2.16，95%置信区间[CI] = [1.14-4.08]；A/H3N2 aGMR = 3.20，95% CI = [1.60-6.39]；B/维多利亚aGMR = 1.91，95% CI = [1.01-3.60]；早期组：A/H1N1 aGMR = 1.03，95% CI = [0.59-1.80]；A/H3N2 aGMR = 1.23，95% CI = [0.68-2.25]；B/维多利亚aGMR = 1.06，95% CI = [0.56-2.03]）。
两剂HD-TIV比SD-QIV具有更高的免疫原性，尤其是在HCT后≥6个月接种时。在整个季节中，两组的滴度均维持在高于基线的水平。
NCT02860039。
