Immune correlates of protection (CoPs) are immunologic biomarkers accepted as a surrogate for an infectious disease clinical endpoint and thus can be used for traditional or provisional vaccine approval. To study CoPs in randomized, placebo-controlled trials, correlates of risk (CoRs) are first assessed in vaccine recipients. This analysis does not assess causation, as a CoR may fail to be a CoP. We propose a causal CoP analysis that estimates the controlled vaccine efficacy curve across biomarker levels $s$, $CVE(s)$, equal to one minus the ratio of the controlled-risk curve $r_C(s)$ at $s$ and placebo risk, where $r_C(s)$ is causal risk if all participants are assigned vaccine and the biomarker is set to $s$. The criterion for a useful CoP is wide variability of $CVE(s)$ in $s$. Moreover, estimation of $r_C(s)$ is of interest in itself, especially in studies without a placebo arm. For estimation of $r_C(s)$, measured confounders can be adjusted for by any regression method that accommodates missing biomarkers, to which we add sensitivity analysis to quantify robustness of CoP evidence to unmeasured confounding. Application to two harmonized phase 3 trials supports that 50% neutralizing antibody titer has value as a controlled vaccine efficacy CoP for virologically confirmed dengue (VCD): in CYD14 the point estimate (95% confidence interval) for $CVE(s)$ accounting for measured confounders and building in conservative margin for unmeasured confounding increases from 29.6% (95% CI 3.5 to 45.9) at titer 1:36 to 78.5% (95% CI 67.9 to 86.8) at titer 1:1200; these estimates are 17.4% (95% CI -14.4 to 36.5) and 84.5% (95% CI 79.6 to 89.1) for CYD15.

翻译：保护( COPs) 的 Immune 相关保护 (CoPs) 是被接受为传染病临床端点的免疫学生物标志, 因此可以用于传统或临时疫苗批准。 要在随机、安慰剂控制的试验中研究COPs, 风险(CoRs) 的相关(CoRs) 首先是在疫苗接受者中进行评估。 本分析没有评估因果关系, 因为COR可能无法成为一个 CoP。 我们提出一个因果 CoP分析, 估计控制疫苗在生物中性水平($, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, Cs, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 美元, 。, 等, 等, 。 等, 等, 等, 等, 等, 等, 等, 等, 等, 等, 等, 。 。 等, 等, 等, 一种, 等, 等, 等, 等, 等, 等, 等, 一种, 一种, 一种, 一种, 美元, 美元, 美元, 一种, 等, 美元, 一种, 等