VALIDATE: Exploiting the synergy between complex intracellular pathogens to expedite vaccine research and development for tuberculosis, leishmaniasis, melioidosis and leprosy.
VALIDATE: Exploiting the synergy between complex intracellular pathogens to expedite vaccine research and development for tuberculosis, leishmaniasis, melioidosis and leprosy.
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DOI：
10.12688/f1000research.14386.1
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
McShane H
中科院分区：
文献类型：
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作者：
Fletcher HA;Chatterjee M;Cooper A;Hussell T;Kaye PM;Prior J;Reljic R;Vermaak S;Vordermeier M;Williams A;McShane H
对于几种复杂的细胞内病原体，我们迫切需要有效的疫苗，但疫苗开发存在共同的障碍。这些疾病，包括结核病、利什曼病、麻风病和类鼻疽病，造成了巨大的疾病负担，对中低收入国家的影响尤为严重。因此，由于受影响人口的边缘化以及投资的预期商业回报率很低，它们往往被忽视。疫苗开发的障碍包括对保护性免疫的不完全理解以及从实验室到临床疫苗试验的转化。目前针对这些病原体的疫苗研究和开发的线性方法涉及基础研究、疫苗设计以及临床前挑战模型和临床试验中的疫苗评价，对于这些复杂的细胞内病原体是低效的。我们建立了一个全球挑战研究基金网络，用于复杂细胞内被忽视的病毒疫苗开发，“VALIDATE”，我们的目标是采用更灵活、综合的跨病原体方法，通过跨病原体分析、跨学科合作以及重复整合人类和动物研究数据，加速这四种病原体的疫苗研究和临床开发。 该网络提供了一个独特的机会，将研究四种典型的复杂细胞内被忽视的病原体（结核分枝杆菌，利什曼原虫属，B。类鼻疽杆菌和麻风分枝杆菌），它们作为巨噬细胞的病原体具有共同的生活方式，诱导类似的终末期病理学并改变宿主免疫和代谢反应。通过这个网络建立的横向合作，以及为早期数据共享提供受保护的环境，将利用这些生物协同作用，通过询问从感染到疾病的机制，我们将能够为这些和其他复杂的细胞内病原体开发共同的疫苗开发策略。
For several complex intracellular pathogens, we have an urgent need for effective vaccines and yet there are common barriers to vaccine development. These diseases, including tuberculosis, leishmaniasis, leprosy and melioidosis, cause a huge burden of disease and disproportionately affect low and middle income countries. They are therefore often neglected due to the marginalisation of affected populations and the poor predicted commercial return on investment. Barriers to vaccine development include an incomplete understanding of protective immunity and translation from the bench into clinical vaccine trials. The current linear approach to vaccine research and development for these pathogens, which involves basic research, vaccine design, and vaccine evaluation in preclinical challenge models and clinical trials, is inefficient for these complex intracellular pathogens. We have established a Global Challenges Research Fund Network for VAccine deveLopment for complex Intracellular neglecteD pAThogEns, “VALIDATE”, where we aim to adopt a more flexible, integrated cross-pathogen approach to accelerate vaccine research and clinical development for these four pathogens, by cross-pathogen analyses, cross-discipline collaborations, and repeated integration of data from human and animal studies. This network provides a unique opportunity to bring together individuals working on four exemplar complex intracellular neglected pathogens ( M.tb, Leishmania spp., B. pseudomallei and M.leprae), which share a common lifestyle as pathogens of macrophages, induce similar end-stage pathologies and alter host immune and metabolic responses. The horizontal collaborations established throughout this network, together with the provision of a protected environment for early data sharing, will exploit these biological synergies. By interrogating mechanisms that lead from infection to disease, we will be able to develop common vaccine development strategies for these and other complex intracellular pathogens.