Improving understanding of lung immunity in tuberculosis to establish a diverse, innovative TB vaccine pipeline targeting mucosal immunity

结核病(TB)仍然是全世界最具破坏性的传染病之一，每天导致4000多人死亡。通过新型疫苗预防结核病感染将为实现世卫组织结束结核病战略和联合国可持续发展目标的目标提供最具成本效益的方法。尽管有希望的结核病候选疫苗寥寥无几，但需要新平台和新战略的创新，以确保开发出最有效和最负担得起的疫苗。TBVACHORIZON将通过追求四个目标来创新和多样化全球结核病疫苗流水线：1.确定结核分枝杆菌感染肺中保护性免疫反应的组成、空间组织和功能。2.评价卡介苗和其他减毒活疫苗黏膜再免疫是否提高了小鼠、非人灵长类和人类对结核病感染的保护效果。3.确定宿主免疫反应谱和肺内天然和疫苗诱导免疫保护的生物标志物。4.支持下一代结核病疫苗的开发，方法是对选定的候选疫苗在动物身上进行标准化的正面测试，并为减毒活疫苗建立新的递送系统、佐剂配方和GMP平台。TBVACHORIZON将增加我们的理解，并开发与肺部免疫保护有关的工具，肺部是结核病感染的主要部位。这些知识将被用来开发粘膜策略，以转化为临床评估和可能的实施。这些相互交织的活动将巩固欧洲在结核病疫苗研究和创新方面的领先地位，最终目标是加快提供负担得起、可获得和更有效的结核病疫苗。

Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide, killing over 4,000 people every day. Prevention of tuberculosisinfection by novel vaccines would provide the most cost-effective approach to achieve the goals of the WHO End TB strategy and the Sustainable Development Goals of the United Nations. While there are few promising TB vaccine candidates available, innovation by new platforms and strategies is needed to ensure that the most effective and affordable vaccines are developed. TBVACHORIZON will innovate and diversify the global TB vaccine pipeline by pursuing four objectives: 1. Define the composition, spatial organisation and functioning of protective immune responses in the Mycobacterium tuberculosis-infected lung. 2. Evaluate whether mucosal re vaccination with BCG and other live attenuated vaccines improves protective efficacy against tuberculosis infection in mice, non-human primates and humans. 3. Identify host immune response profiles and biomarkers of natural and vaccine-induced immune protection in the lung. 4. Support next generation TB vaccine development by standardised head-to-head testing of selected vaccine candidates in animals and the establishment of novel delivery systems, adjuvant formulations and GMP platforms for live attenuated vaccines. TBVACHORIZON will increase our understanding and develop tools pertaining to immune protection in the lung, the major site of tuberculosis infection. This knowledge will be exploited to develop mucosal strategies for translating towards clinical evaluation and possible implementation. The interwoven activities will consolidate Europe’s leading role in TB vaccine research and innovation, with the ultimate goal of accelerated availability of affordable, accessible and more effective TB vaccines.