Determining the effect of vaccine-induced immune response on disease risk is an important goal of vaccinology. Typically, immune correlates analyses are conducted prospectively with immune response measured shortly after vaccination and subsequent disease status regressed on immune response. In outbreaks and rare disease settings, collecting samples from all vaccinees is not feasible. The test negative design is a retrospective design used to measure vaccine efficacy where symptomatic individuals who present at a clinic are assessed for relevant disease (cases) or some other disease (controls) and vaccination status ascertained. This article proposes that test negative vaccinees have immune response to vaccine assessed both for relevant (e.g., Ebola) and irrelevant (e.g., vector) proteins. If the latter immune response is unaffected by active (Ebola) infection, and is correlated with the relevant immune response, it can serve as a proxy for the immune response of interest proximal to infection. We show that logistic regression using imputed immune response as the covariate and case disease as outcome can estimate the prospective immune response slope and detail the assumptions needed for unbiased inference. The method is evaluated by simulation under various scenarios including constant and decaying immune response. A simulated dataset motivated by ring vaccination for an ongoing Ebola outbreak is analyzed.

中文翻译：

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使用来自测试阴性设计的疫苗接种者进行免疫相关分析。

确定疫苗诱导的免疫反应对疾病风险的影响是疫苗学的一个重要目标。通常，免疫相关分析是前瞻性地进行的，在接种疫苗后不久测量免疫反应，随后的疾病状态在免疫反应上退化。在暴发和罕见病环境中，从所有疫苗接种者身上采集样本是不可行的。测试阴性设计是一种用于测量疫苗效力的回顾性设计，其中对出现在诊所的有症状个体进行相关疾病（病例）或其他疾病（对照）评估并确定疫苗接种状态。本文提出，测试阴性的疫苗接种者对疫苗的免疫反应进行了相关（例如，埃博拉病毒）和不相关（例如，载体）蛋白的评估。如果后一种免疫反应不受活动性（埃博拉）感染的影响，并且与相关的免疫反应相关，它可以作为感染附近感兴趣的免疫反应的代理。我们表明，使用估算免疫反应作为协变量和病例疾病作为结果的逻辑回归可以估计预期免疫反应斜率并详细说明无偏推断所需的假设。该方法通过模拟在各种情况下进行评估，包括恒定和衰减的免疫反应。分析了针对正在进行的埃博拉病毒爆发的环形疫苗接种驱动的模拟数据集。我们表明，使用估算免疫反应作为协变量和病例疾病作为结果的逻辑回归可以估计预期免疫反应斜率并详细说明无偏推断所需的假设。该方法通过模拟在各种情况下进行评估，包括恒定和衰减的免疫反应。分析了针对正在进行的埃博拉病毒爆发的环形疫苗接种驱动的模拟数据集。我们表明，使用估算免疫反应作为协变量和病例疾病作为结果的逻辑回归可以估计预期免疫反应斜率并详细说明无偏推断所需的假设。该方法通过模拟在各种情况下进行评估，包括恒定和衰减的免疫反应。分析了针对正在进行的埃博拉病毒爆发的环形疫苗接种驱动的模拟数据集。