Data from: Influenza hemagglutination-inhibition antibody titer as a mediator of vaccine-induced protection for influenza B

Background: The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine, but the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed. Methods: We used data from a randomized placebo-controlled trial of a split-virion inactivated influenza vaccine in children 6-17 years of age. 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. Results: We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% CI: 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection. Conclusions: The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination, but 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.

背景：血凝抑制（hemagglutination inhibition, HAI）试验是灭活流感疫苗保护效力的公认相关替代标志物，但疫苗诱导的保护作用中有多大比例由接种后HAI抗体滴度介导，目前尚未得到评估。
方法：本研究纳入一项针对6-17岁儿童的裂解灭活流感疫苗随机安慰剂对照试验数据。在接种疫苗或安慰剂前及接种后30天采集血清，通过HAI试验针对B/Brisbane/60/2008样毒株（B/Victoria谱系）进行检测。我们构建Cox比例风险模型以分析实验室确诊乙型流感的发病时间，并采用因果中介分析估算由更高HAI滴度介导的疫苗总保护效应占比。
结果：本研究估算显示，疫苗针对确诊B/Victoria谱系感染的效力为68%（95%置信区间（confidence interval, CI）：33%~88%），接种后HAI滴度可解释57%的疫苗保护效应。
结论：儿童接种灭活流感疫苗的多数保护效应由接种后升高的HAI滴度介导，但疫苗接种诱导的免疫应答其他组分也可能参与保护作用，有待进一步研究。因果中介分析为量化各类保护中介物的作用提供了研究框架。