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

结核病仍然是全世界最具破坏性的传染病之一，每天造成4,000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终结结核病战略的目标和联合国可持续发展目标提供最具成本效益的方法。虽然目前几乎没有有希望的结核病候选疫苗，但需要通过新的平台和战略进行创新，以确保开发出最有效和最负担得起的疫苗。TBVACHORIZON将通过追求以下四个目标来创新和多样化全球结核病疫苗管道：1.定义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.评估卡介苗和其他减毒活疫苗的粘膜再接种是否能提高小鼠、非人灵长类动物和人类对结核病感染的保护效力。3.确定宿主免疫应答特征和肺中天然和疫苗诱导的免疫保护的生物标志物。4.通过在动物身上对选定的候选疫苗进行标准化的头对头试验，并为减毒活疫苗建立新的给药系统、佐剂配方和GMP平台，支持下一代结核病疫苗的开发。TBVACHORIZON将增加我们对肺（结核感染的主要部位）免疫保护的理解并开发相关工具。将利用这些知识制定粘膜策略，用于临床评价和可能的实施。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导作用，最终目标是加速提供负担得起、可及且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 revaccination 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.