Innovations for vaccines against helminth infections

寄生虫（蠕虫）感染继续造成巨大的全球健康负担。然而，不存在能够控制和消除蠕虫感染的有效疫苗。其主要原因是，目标发现方法没有得到很好的开发，保护性免疫机制充其量只是部分阐明，没有针对特定蠕虫疫苗要求的生产平台，并且通常缺乏用于选择和快速进展临床前和临床候选疫苗的管道。此外，控制人类感染模型现在才被开发和优化的一些最重要的人类蠕虫。迄今为止，这些模型尚未在疫苗开发计划中广泛实施。WORMVACS2.0的目标是建立一个有效的管道，以支持蠕虫疫苗开发，重点是寄生虫和钩虫，并最终控制和消除世界上一些最具破坏性和持久性的被忽视的热带病（NTD）。我们的目标是通过开发和应用一种创新的方法来实现这一目标，该方法利用受控的人类感染模型、蠕虫疫苗/疫苗抗原生产的新平台、实验动物模型和改进的靶点发现方法，该方法应用最先进的免疫学分析来识别保护的相关性和特征。WORMVACS2.0将推进对蠕虫感染的宿主免疫的科学和临床知识，应用创新和可持续的平台技术，为全球重要的蠕虫感染的下一代有效疫苗量身定制。该项目将生产一系列多样化的钩虫和寄生虫候选疫苗，准备进行临床试验，并进行第一阶段临床试验，以推进基于mRNA平台的血吸虫病疫苗。

Infections with parasitic worms (helminths) continue to cause a massive global health burden. Yet, effective vaccines to enable control and elimination of helminth infections do not exist. Primary reasons for this are that target discovery approaches are not well developed, protective immune mechanisms are only partially clarified at best, production platforms tailored to specific helminth vaccine requirements are not available, and a pipeline for selecting and rapidly progressing pre-clinical and clinical vaccine candidates is generally lacking. Moreover, controlled human infection models are only now being developed and optimized for some of the most important human helminths. These models have not yet been widely implemented in vaccine development programs to date. The objective of WORMVACS2.0 isto establish an effective pipeline to support helminth vaccine development focusing on schistosomes and hookworms, and ultimately the control and elimination of some of the world’s most devastating and persistent Neglected Tropical Diseases (NTDs). We aim to achieve this through the development and application of an innovative approach leveraging controlled human infectionmodels, novel platforms for helminth vaccine/vaccine antigen production, experimental animal models, and improved target discovery methodology applying state-of-the-art immunological profiling to identify correlates and signatures of protection. WORMVACS2.0 will advance scientific and clinical knowledge of host immunity in response to helminth infection, apply innovative and sustainable platform technologies tailored to the next generation of effective vaccines against helminth infections of global importance. The project will produce a diversified portfolio of hookworm and schistosome vaccine candidates ready for progressing to clinical testing and conduct a phase 1 clinical trial to advance an mRNA platform based schistosomiasis vaccine.