Background The hemagglutination inhibition antibody (HAI) titer mediates only a part of vaccine-induced protection against influenza virus infections. Using causal mediation analysis, we quantified the proportion of vaccine efficacy mediated by post-vaccination HAI titers. Methods Causal mediation analyses were conducted using data collected for a randomized, active-comparator controlled, phase 3 trial of a candidate inactivated, split-virion seasonal quadrivalent influenza vaccine (QIV) in children aged 3 to 8 years conducted from October 2010 to December 2011 in eight countries. Vaccine efficacy was estimated with a weighted Cox proportional hazards regression model. Estimates were decomposed into the direct and indirect effects mediated by post-vaccination HAI titers. Results The proportions of vaccine efficacy mediated by post-vaccination HAI titers were estimated to be 22% (95% CI: 18%, 47%) for influenza A(H1N1), 20% (95% CI: 16%, 39%) for influenza A(H3N2), and 37% (95% CI: 26%, 85%) for influenza B/Victoria. Conclusions HAI titers partially mediate influenza vaccine efficacy against influenza A(H1N1), A(H3N2), and B/Victoria. Our estimates were lower than previous studies, possibly reflecting expected heterogeneity in antigenic similarity between vaccine and circulating viruses across seasons. Data from more influenza seasons are needed to understand better the mediating effects of HAI titers on vaccine efficacy.

中文翻译：

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血凝抑制抗体滴度介导流感疫苗针对有症状的甲型 (H1N1)、甲型 (H3N2) 和乙型/维多利亚型流感感染的功效

背景 血凝抑制抗体 (HAI) 滴度仅介导疫苗诱导的针对流感病毒感染的部分保护作用。通过因果中介分析，我们量化了由疫苗接种后 HAI 滴度介导的疫苗功效比例。方法 使用 2010 年 10 月至 2011 年 12 月在 3 至 8 岁儿童中进行的候选灭活分裂病毒颗粒季节性四价流感疫苗 (QIV) 的随机、活性对照对照 3 期试验收集的数据进行因果中介分析。在八个国家。使用加权 Cox 比例风险回归模型评估疫苗功效。估计值被分解为由疫苗接种后 HAI 滴度介导的直接和间接影响。结果 接种后 HAI 滴度介导的疫苗效力比例估计为：甲型 H1N1 流感 22%（95% CI：18%、47%）、20%（95% CI：16%、39%）甲型流感 (H3N2) 为 37%（95% CI：26%、85%）。结论 HAI 滴度部分调节流感疫苗针对甲型 (H1N1)、甲型 (H3N2) 和乙型/维多利亚型流感的功效。我们的估计低于以前的研究，可能反映了疫苗和跨季节传播病毒之间抗原相似性的预期异质性。需要更多流感季节的数据来更好地了解 HAI 滴度对疫苗功效的中介作用。