Fold Rise in Antibody Titers by Measured by Glycoprotein-Based Enzyme-Linked Immunosorbent Assay Is an Excellent Correlate of Protection for a Herpes Zoster Vaccine, Demonstrated via the Vaccine Efficacy Curve
Fold Rise in Antibody Titers by Measured by Glycoprotein-Based Enzyme-Linked Immunosorbent Assay Is an Excellent Correlate of Protection for a Herpes Zoster Vaccine, Demonstrated via the Vaccine Efficacy Curve
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DOI：
10.1093/infdis/jiu279
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发表时间：
2014-11-15
影响因子：
6.4
通讯作者：
Chan, Ivan S. F.
中科院分区：
文献类型：
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作者：
Gilbert, Peter B.;Gabriel, Erin E.;Chan, Ivan S. F.
背景。在50-59岁的人群中，1剂许可带状疱疹疫苗（ZV; Zostavax; Merck）的III期Zostavax有效性和安全性试验显示，约70%的疫苗有效性（VE）可以降低带状疱疹（HZ）的发病率。该试验的目的是通过基于糖蛋白的酶联免疫吸附试验来评估免疫反应生物标志物（测量水痘带状疱疹病毒（VZV）抗体）作为免疫保护（CoPs）的相关因素。主要分层疫苗功效曲线框架用于统计评估免疫反应生物标志物，如CoPs。VE曲线描述了VE相对于临床终点（HZ）在参与者亚组之间的变化情况，这些亚组由测量疫苗诱导免疫反应的生物标志物读数定义。使用几个亚组定义估计VE曲线。从免疫前到免疫后6周VZV抗体滴度的翻倍上升是一个很好的CoP， VE随着翻倍的上升而急剧上升：在没有上升的亚组中，VE估计为0%，在上升5.26倍的亚组中，VE估计为90%。相比之下，免疫后6周测量的VZV抗体滴度不能预测VE，不同滴度亚组的估计VE相似。该分析说明了VE曲线框架在疫苗功效试验中评估免疫反应生物标志物作为cop的价值。
Background. The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50-59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkersmeasuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ.Methods. The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions.Results. The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups.Conclusions. The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials.