Postvaccination Serum Antirotavirus Immunoglobulin A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings
Postvaccination Serum Antirotavirus Immunoglobulin A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings
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DOI：
10.1093/infdis/jiaa068
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发表时间：
2020-07-15
影响因子：
6.4
通讯作者：
Lopman, Benjamin A.
中科院分区：
文献类型：
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作者：
Baker, Julia M.;Tate, Jacqueline E.;Lopman, Benjamin A.
背景对轮状病毒胃肠炎保护的相关性将有助于快速评估疫苗接种策略和下一代轮状病毒疫苗。我们的目的是量化疫苗接种后血清抗轮状病毒免疫球蛋白A（伊加）的阈值，作为个体水平的免疫相关保护轮状病毒胃炎。汇总了来自16个国家的9项GlaxoSmithKline Rotarix 2/3期临床试验中5074名婴儿的个体水平数据。采用考克斯比例风险模型估计伊加阈值与轮状病毒性胃炎发生率之间关系的风险比。血清转化（伊加>= 20 U/mL）对1岁以下的任何严重轮状病毒胃肠炎都有实质性保护作用。在儿童死亡率低的情况下，血清转换提供了几乎完美的保护，防止严重的轮状病毒胃肠炎（风险比，0.04; 95%置信区间[CI]，0.01 - 0.31）。在儿童死亡率高的情况下，血清转换显著降低了严重轮状病毒胃肠炎的风险（HR，0.46; 95%CI，0.25 - 0.86）。随着伊加阈值的增加，轮状病毒胃肠炎的风险普遍降低。一个给定的伊加阈值提供了更好的保护，在低相比，高儿童死亡率设置。接种后抗轮状病毒伊加是一个有价值的相关保护轮状病毒胃肠炎1岁。血清转化为评估轮状病毒疫苗性能提供了一个信息阈值。
Background. A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis.Methods. Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis.Results. Seroconversion (IgA >= 20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR, 0.04; 95% confidence interval [CI], .01-.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI, .25-.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings.Discussion. Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance.