Cowling Benjamin J, Wong Sook-San, Santos Jefferson J S, Touyon Lisa, Ort Jordan, Ye Naiqing, Kwok Natalie K M, Ho Faith, Cheng Samuel M S, Ip Dennis K M, Peiris Malik, Webby Richard J, Wilson Patrick C, Valkenburg Sophie A, Tsang John S, Leung Nancy H L, Hensley Scott E, Cobey Sarah
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Laboratory of Data Discovery for Health Limited, Hong Kong Science and Technology Park, New Territories, Hong Kong Special Administrative Region, China.
medRxiv. 2024 May 17:2024.05.16.24307455. doi: 10.1101/2024.05.16.24307455.
Studies have reported that repeated annual vaccination may influence the effectiveness of the influenza vaccination in the current season. The mechanisms underlying these differences are unclear but might include "focusing" of the adaptive immune response to older strains.
We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. Participants were randomized equally between five groups, with planned annual receipt of vaccination (V) or saline placebo (P) as follows: P-P-P-P-V, P-P-P-V-V, P-P-V-V-V, P-V-V-V-V, or V-V-V-VV. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera were tested by hemagglutination inhibition assays, focus reduction neutralization tests and enzyme-linked immunosorbent assays against vaccine strains.
From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. We selected sera from 95 participants at five timepoints from the first two study years for testing. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with substantial increases for first-time vaccinees and smaller increases for repeat vaccinees, who had higher pre-vaccination titers in year 2. There were statistically significant reductions in the proportion of participants achieving a four-fold greater rise in antibody titer for the repeat vaccinees for A(H1N1), B/Victoria and B/Yamagata, but not for influenza A(H3N2). There were no statistically significant differences between groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains.
In the first two years, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection. The vaccine strains of A(H1N1) and A(H3N2) were updated in year 2, providing an opportunity to explore antigenic distances between those strains in humans in subsequent years.
研究报告称，每年重复接种疫苗可能会影响当季流感疫苗的有效性。这些差异背后的机制尚不清楚，但可能包括适应性免疫反应对较旧毒株的“聚焦”。
我们在18至45岁的成年人中开展了一项为期5年的重复流感疫苗接种（Flublok，赛诺菲巴斯德公司生产）随机安慰剂对照试验。参与者被平均随机分为五组，计划每年接受疫苗接种（V）或生理盐水安慰剂（P），分组如下：P-P-P-P-V、P-P-P-V-V、P-P-V-V-V、P-V-V-V-V或V-V-V-V-V。每年在接种疫苗前以及接种后30天和182天采集血清样本。通过血凝抑制试验、蚀斑减少中和试验和酶联免疫吸附试验对一部分血清样本进行针对疫苗毒株的检测。
从2020年10月23日至2021年3月11日，我们招募了447名成年人并进行随机分组。我们从前两个研究年度的五个时间点选取了95名参与者的血清进行检测。在接种疫苗的个体中，针对每种疫苗毒株，抗体滴度在第0天至第30天之间均有所增加，首次接种疫苗者的抗体滴度大幅增加，而重复接种疫苗者的抗体滴度增加幅度较小，后者在第2年接种前的滴度较高。对于A(H1N1)、B/维多利亚系和B/山形系毒株，重复接种疫苗者抗体滴度升高四倍的参与者比例有统计学显著下降，但对于甲型H3N2流感毒株则没有。在第30天，各疫苗毒株的几何平均滴度或抗体滴度≥40的参与者比例在各组之间没有统计学显著差异。
在头两年，重复接种疫苗者和首次接种疫苗者针对所有四种疫苗毒株的接种后几何平均滴度相似，表明临床保护水平相似。A(H1N1)和A(H3N2)的疫苗毒株在第2年进行了更新，为后续年份探索这些毒株在人体内的抗原距离提供了机会。
