World Health Organization 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.
Statistics Department, Wharton School, University of Pennsylvania, Philadelphia.
Clin Infect Dis. 2019 May 2;68(10):1713-1717. doi: 10.1093/cid/ciy759.
The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine. However, the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed.
We used data from a randomized, placebo-controlled trial of a split-virion inactivated influenza vaccine in children aged 6-17 years. Sera were collected before and 30 days after receipt of vaccination or placebo and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria lineage). We fitted Cox proportional hazards models to the time to laboratory-confirmed influenza B. We used causal mediation analysis to estimate the proportion of the total effect of vaccination that was mediated by higher HAI titers.
We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% confidence interval, 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection.
The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination; however, other components of the immune response to vaccination may also play a role in protection and should be further explored. Causal mediation analysis provides a framework to quantify the role of various mediators of protection.
血凝抑制（HAI）试验是已建立的灭活流感疫苗保护相关性指标。然而，疫苗接种后 HAI 滴度介导的疫苗保护比例尚未得到评估。
我们使用了一项在 6-17 岁儿童中进行的分裂病毒灭活流感疫苗随机、安慰剂对照试验的数据。在接种或安慰剂接种前和 30 天后采集血清，并通过 HAI 试验针对 B/Brisbane/60/2008 样（B/维多利亚谱系）进行检测。我们使用 Cox 比例风险模型拟合了实验室确诊乙型流感的时间。我们使用因果中介分析来估计疫苗接种总效果中由更高的 HAI 滴度介导的比例。
我们估计疫苗对确诊的 B/维多利亚感染的疗效为 68%（95%置信区间，33%，88%），接种后 HAI 滴度解释了疫苗保护作用的 57%。
儿童中灭活流感疫苗的大部分效果是通过接种后 HAI 滴度的增加来介导的；然而，疫苗免疫反应的其他成分也可能在保护中发挥作用，应进一步探索。因果中介分析提供了一个量化各种保护中介作用的框架。
