Kelkar Natasha S, Curtis Nicholas C, Lahey Timothy P, Wieland-Alter Wendy, Stout Jason E, Larson Erica C, Jauro Solomon, Scanga Charles A, Darrah Patricia A, Roederer Mario, Seder Robert A, von Reyn C Fordham, Lee Jiwon, Ackerman Margaret E
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
bioRxiv. 2024 Dec 9:2024.12.05.627012. doi: 10.1101/2024.12.05.627012.
Development of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection against (Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)-immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain () sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB. In humans, antibodies to MOS also scale with vaccine dose, are elicited by BCG vaccination, are observed during TB disease, and demonstrate cross-reactivity with Mtb; in NHP, MOS-specific antibodies scale with dose and serve as a CoP mediated by BCG vaccination. Collectively, this study reports a novel humoral CoP and specific antigenic targets that may be relevant to achieving vaccine-mediated protection from TB.
对提供抗结核分枝杆菌（Mtb）保护作用的特定因素认识不足以及缺乏已知的保护关联指标（CoP），给开发有效的结核病（TB）疫苗带来了挑战。我们结合了来自一种显示出疗效的疫苗（DarDar [NCT00052195]）以及卡介苗（BCG）免疫的人类和非人灵长类动物（NHP）的样本，确定了一种跨物种和疫苗接种方案的体液CoP。针对DarDar疫苗株（）超声裂解物（MOS）的特异性抗体与免受确诊结核病疗效终点的保护相关。在人类中，针对MOS的抗体也随疫苗剂量增加，由卡介苗接种引发，在结核病发病期间可观察到，并且与结核分枝杆菌表现出交叉反应性；在非人灵长类动物中，针对MOS的特异性抗体随剂量增加，并作为卡介苗接种介导的CoP。总体而言，本研究报告了一种新型体液CoP和特定抗原靶点，它们可能与实现疫苗介导的结核病保护相关。
