Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.
Vaccine. 2021 Feb 22;39(8):1339-1348. doi: 10.1016/j.vaccine.2020.11.051. Epub 2021 Jan 21.
The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults.
479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose.
Subjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis.
MF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.
自 2013 年以来，人类甲型流感（H7N9）感染病例不断增加，死亡率居高不下。我们进行了一项 II 期、随机、部分盲法试验，以评估不同剂量和方案下接种 MF59 佐剂的甲型 H7N9 流感灭活、分裂病毒疫苗（H7N9 IIV）在老年人中的安全性和免疫原性。
479 名健康状况稳定、年龄≥65 岁的成年人被随机分为六组中的一组，接受 3.75、7.5 或 15µg 的甲型流感/上海/2013（H7N9）IIV 疫苗，用 MF59 佐剂，采用三剂系列，分别在第 1、28 和 168 天或第 1、57 和 168 天接种。在每次接种前和接种后 28 天，使用血凝抑制（HAI）和微量中和（MN）试验评估免疫原性。安全性评估在最后一剂后 1 年进行。
所有组的受试者仅有适度的免疫反应，第二次疫苗接种后 HAI GMT<20，第三次疫苗接种后 HAI GMT<29。第二次接种后，<37%的受试者 HAI 滴度≥40，第三次接种后，<49%的受试者 HAI 滴度≥40。两种剂量方案之间无显著差异。MN 滴度也呈现类似的模式，尽管滴度比 HAI 滴度高约两倍。逻辑回归模型表明，免疫反应与年龄、性别或体重指数之间无统计学显著关联，而最近接种季节性流感疫苗显著降低了 HAI 反应[比值比 0.13（95%可信区间 0.05，0.33）；p<0.001]。总体而言，疫苗耐受性良好。发生了两例轻度潜在免疫介导的不良事件，分别为扁平苔藓和点滴状银屑病。
在老年人群中，接种三剂 MF59 佐剂的 H7N9 IIV 后，免疫原性仅适度。在不同抗原剂量或两种剂量方案之间，抗体反应无显著差异。
