Methods for Immune Biomarkers Measurement, Preprocessing and Association Studies

 描述（由申请人提供）：寻找疫苗诱导的免疫应答生物标志物，预测疫苗对HIV-1和其他重要病原体感染的保护作用，并了解其作为保护机制的作用，是疫苗研究的重要组成部分。我们在免疫相关性研究中区分了三个阶段。第一阶段涉及免疫反应的测量，可能涉及实验设计。第二阶段对第一阶段中获得的免疫应答生物标志物进行预处理以形成复合生物标志物。第三阶段检查临床结果与免疫应答生物标志物之间的关联。我们将为三个目标中的每个阶段开发新的统计方法，以减少免疫反应测量中的噪声（目标1和2），减少多重测试负担（目标2），提高保护所需的免疫反应阈值的估计（目标3），并提高识别非线性免疫相关性的能力（目标3）。此外，我们将开发HIV-1包膜蛋白序列分析的统计方法（子目标3（iii）），以深入了解免疫相关功能的机制，以及广泛中和抗体识别HIV-1的机制。

 DESCRIPTION (provided by applicant): Finding vaccine-induced immune response biomarkers that predict vaccine-protection against HIV-1 and other significant pathogen infection, and understanding their role as mechanisms of protection, is an essential part of the vaccine research. We distinguish between three stages in the study of immune correlates. The first stage deals with measurement of immune response and may involve design of experiments. The second stage performs preprocessing of immune response biomarkers obtained in the first stage to form composite biomarkers. The third stage examines the association between clinical outcome and immune response biomarkers. We will develop novel statistical methods for each stage in each of the three aims in order to reduce noise in immune response measurements (Aim 1 & 2), reduce multitesting burden (Aim 2), improve estimation of immune response thresholds required for protection (Aim 3), and improve the power for identifying nonlinear immune correlates (Aim 3). In addition, we will develop statistical methods for HIV-1 envelope protein sequence analysis (subaim 3(iii)) to gain insight into the mechanisms of immune correlates function, as well as the mechanisms of HIV-1 recognition by broadly neutralizing antibodies.