University of Washington Arboviral Research Network (UWARN)

摘要：联合世界抗病毒研究网络(UWARN，前身为华盛顿大学虫媒病毒研究网络)将通过对虫媒病毒进行研究，以应对新出现的和再次出现的传染病，其中包括目前高负担的病原体，包括登革热、基孔肯雅热和寨卡病毒。虫媒病毒还包括新出现和重新出现的病毒，如Mayaro、Una、Usutu、日本脑炎、黄热病、克里米亚-刚果出血热和Oropouche病毒。UWARN将利用UW大流行疾病防备联盟(前身为Metacenter)和在巴西、塞内加尔、南非、巴基斯坦和台湾的强大研究实验室合作伙伴以及UW全球卫生部在能力建设方面的全球影响力。UWARN国际合作伙伴已经建立了基于机构和基于人群的队列，以执行计划的研究和监测新病毒的出现。拟议的UWARN研究将创造新的人类病毒中和单抗(HU-nMabs)，可用于治疗或诊断。UWARN的研究还将创造新的诊断方法，由蛋白质设计研究所从头开始创造，作为人造蛋白质，当体液中存在病毒抗体时释放光线。最后，UWARN的研究将产生对病毒如何操纵人类先天免疫系统的理解，这些信息将被用于设计生物标记物来预测严重疾病，并建议宿主导向的治疗方法，从而在虫媒病毒感染后产生更好的结果。提议的技术是通用的，可以迅速适应未来出现的任何虫媒病毒威胁。UWARN的合作者涵盖病毒学、细菌学、真菌学和寄生虫感染，因此UWARN可以应对各种新出现的传染病威胁。UWARN国际实验室拥有先进的能力，包括带有发电机动力备份-80C冰柜的生物储存库、下一代测序(NGS)能力、荧光细胞分选和BSL-3密封设施。UWARN队列已经将来自患有已知和未知虫媒病毒疾病的急性发热性疾病期间的个人的样本保存在生物库中，伙伴关系站点正在为未来的人口和设施样本收集做好准备。UWARN实验室将使用元基因组NGS来检测附属队列中出现的新病毒。UWARN合作伙伴有昆虫学家和兽医合作，根据需要对节肢动物病媒和动物宿主进行采样。其他创新能力包括巴西UWARN合作伙伴的移动面包车，具有车载NGS功能，可在不到18小时的时间内进行实时、现场病毒测序和采样，直至病毒鉴定。第二个合作伙伴，塞内加尔的IRESSEF，计划在塞内加尔建立一个类似的移动工具，用于病毒采样和测序，巴西集团将在技术转让和最佳实践方面与IRESSEF合作。UWARN的合作伙伴将作为其他新兴传染病研究中心(EIDRC)的资源，提供单抗、蛋白质设计和宿主导向疗法方面的专业知识。

Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facility–based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.