Innovations for vaccines against helminth infections

感染寄生虫(蠕虫)继续造成巨大的全球健康负担。然而，目前尚不存在能够控制和消除蠕虫感染的有效疫苗。造成这种情况的主要原因是，靶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能部分阐明，没有针对特定蠕虫疫苗要求量身定做的生产平台，以及普遍缺乏选择和快速推进临床前和临床候选疫苗的管道。此外，针对一些最重要的人类蠕虫，受控人类感染模型现在才刚刚开发和优化。到目前为止，这些模型还没有在疫苗开发项目中广泛实施。WORMVACS2.0的目标是建立一个有效的渠道，支持以血吸虫和钩虫为重点的蠕虫疫苗的开发，并最终控制和消除一些世界上最具破坏性和持续被忽视的热带病(NTDS)。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点，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目标发现方法，应用最先进的免疫图谱来识别相关保护和保护信号。WORMVACS2.0将促进宿主免疫的科学和临床知识，以应对蠕虫感染，应用创新和可持续的平台技术，为下一代具有全球重要性的蠕虫感染有效疫苗量身定做。该项目将生产多样化的钩虫和血吸虫候选疫苗组合，为进入临床测试做好准备，并进行第一阶段临床试验，以推进基于信使核糖核酸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.