Huang Ying, Follmann Dean
Biostatistics, Bioinformatics and Epidemiology Program, Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109.
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, 5601, MA.
Biostatistics. 2024 Dec 31;26(1). doi: 10.1093/biostatistics/kxae031.
Immune response decays over time, and vaccine-induced protection often wanes. Understanding how vaccine efficacy changes over time is critical to guiding the development and application of vaccines in preventing infectious diseases. The objective of this article is to develop statistical methods that assess the effect of decaying immune responses on the risk of disease and on vaccine efficacy, within the context of Cox regression with sparse sampling of immune responses, in a baseline-naive population. We aim to further disentangle the various aspects of the time-varying vaccine effect, whether direct on disease or mediated through immune responses. Based on time-to-event data from a vaccine efficacy trial and sparse sampling of longitudinal immune responses, we propose a weighted estimated induced likelihood approach that models the longitudinal immune response trajectory and the time to event separately. This approach assesses the effects of the decaying immune response, the peak immune response, and/or the waning vaccine effect on the risk of disease. The proposed method is applicable not only to standard randomized trial designs but also to augmented vaccine trial designs that re-vaccinate uninfected placebo recipients at the end of the standard trial period. We conducted simulation studies to evaluate the performance of our method and applied the method to analyze immune correlates from a phase III SARS-CoV-2 vaccine trial.
免疫反应会随时间衰减，疫苗诱导的保护作用通常也会减弱。了解疫苗效力如何随时间变化对于指导疫苗在预防传染病方面的研发和应用至关重要。本文的目的是在基线无免疫的人群中，在对免疫反应进行稀疏采样的Cox回归背景下，开发统计方法来评估免疫反应衰减对疾病风险和疫苗效力的影响。我们旨在进一步厘清时变疫苗效应的各个方面，无论是对疾病的直接影响还是通过免疫反应介导的影响。基于一项疫苗效力试验的事件发生时间数据以及纵向免疫反应的稀疏采样，我们提出了一种加权估计诱导似然方法，该方法分别对纵向免疫反应轨迹和事件发生时间进行建模。这种方法评估免疫反应衰减、峰值免疫反应和/或疫苗效力减弱对疾病风险的影响。所提出的方法不仅适用于标准随机试验设计，也适用于在标准试验期结束时对未感染的安慰剂接受者进行再接种的强化疫苗试验设计。我们进行了模拟研究以评估我们方法的性能，并应用该方法分析了一项III期SARS-CoV-2疫苗试验中的免疫相关性。
