Development of a VLP vaccine for the emerging viral pathogen Enterovirus D68

这一申请涉及EV-D68疫苗的开发，这是一种具有重大大流行潜力的病毒。这种病毒是导致AFM的原因之一，AFM是一种危及生命的疾病，90%的幸存者患有长期的肌肉无力。2014年在美国爆发的疫情导致1395例确诊感染，欧洲和美国现在都建立了EV-D68监测网络。已在若干国家观察到AFM病例，包括西非7个国家的567例病例。EV-D68病例正在增加，全球大部分地区都发生季节性疫情，这对低收入和中等收入国家来说尤其令人担忧，因为持续的医疗需求给卫生保健、资源和基础设施带来了沉重负担。目前还没有针对EV-D68的疫苗或获得许可的治疗方法，然而，研究表明，病毒样颗粒（VLP）疫苗可能是有效的。作为世卫组织资助的一个项目的一部分，我们的小组成功地为密切相关的脊髓灰质炎病毒开发了VLP疫苗。这些VLP疫苗旨在取代目前的脊髓灰质炎病毒疫苗，目前的技术需要生产大量的脊髓灰质炎病毒，这是一个重大的生物安全问题，VLP疫苗被认为是理想的替代品。VLPs由病毒结构蛋白组成，这些结构蛋白组装成类似于病毒但不含遗传物质的颗粒。这意味着vlp可以被免疫系统识别，但不能引起感染，这种疫苗是提供疫苗诱导保护的安全有效的方法。该项目建立在成功开发有关病毒的VLP项目期间获得的经验基础上，并将朝着临床前免疫试验的方向发展，以证明疫苗的有效性。EV-D68 VLPs的生产将在酵母中进行，因为这是一种低成本且易于扩展的工艺。我们已经使用该系统生产脊髓灰质炎病毒VLP候选疫苗，并已开始将该技术转让给LMIC制造商。作为脊髓灰质炎VLP项目的一部分，我们还与这些合作伙伴协调，开发适合工业规模生产的净化方法。我们已经研究了多种疫苗配方，以评估我们的VLPs在各种储存条件下的稳定性。疫苗开发的这一方面对于在冷链维护可能具有挑战性的地区开展疫苗运动尤其重要。

This application concerns the development of a vaccine against EV-D68, a virus with significant pandemic potential. This virus is one of the causes of AFM, a life-threatening condition from which 90% of survivors have long-lasting muscle weakness. An outbreak in the USA in 2014 resulted in 1395 confirmed infections, and both Europe and the United States now have established EV-D68 surveillance networks. Cases of AFM have been observed across several countries, including 567 cases across 7 countries in West Africa. Cases of EV-D68 are increasing, with seasonal outbreaks occurring across much of the globe, this is of particular concern for LMIC where the ongoing medical needs place a substantial burden on healthcare, resources, and infrastructure.There are no current vaccines or licensed treatments available for EV-D68, however, studies have suggested that a virus-like particle (VLP) vaccine is likely to be effective. As part of a WHO-funded project, our team have successfully developed VLP vaccines for the closely related poliovirus. These VLP vaccines are intended to replace the current poliovirus vaccines, the current technology requires the manufacture of large quantities of poliovirus, which is a significant biosafety concern and VLP vaccines are considered an ideal replacement.VLPs consist of viral structural proteins, these assemble into a particle which resembles the virus but contains no genetic material. This means that the VLPs can be recognised by the immune system but are not capable of causing an infection, such a vaccine is a safe and effective way to provide vaccine-induced protection.This project is built on experience acquired during the successful development of VLP projects on related viruses and will progress towards pre-clinical immunisation trials to demonstrate the effectiveness of the vaccines. Production of EV-D68 VLPs will be in yeast as this is a low-cost and easily scalable process. We have already used this system to produce a poliovirus VLP vaccine candidate and have begun the process of transfer of this technology to LMIC manufacturers. As part of our polio VLP project, we have also coordinated with these partners to develop purification methods that are amenable to industrial-scale production.We have investigated a variety of vaccine formulations to assess the stability of our VLPs under a variety of storage conditions. This aspect of vaccine development is particularly significant for vaccine campaigns in regions where maintenance of cold chain may be challenging.