Exploitation of x-ray irradiated viruses for vaccine development (XVacc)

几十年来，许多成功使用的疫苗都依赖于灭活致病物质使其不具有传染性。这种方法的一个好处是接受者的免疫系统“看到”整个病原体，因此产生的免疫力将被激发，为暴露于活病原体做准备。寨卡病毒灭活疫苗（PIV）是一种新型的疫苗，可在多种抗原上产生免疫力，具有快速的可扩展性，已知的安全性和成本效益。最近开发的针对寨卡病毒的纯化灭活病毒（PIV）疫苗在包括非人类灵长类动物在内的动物模型中显示出保护作用，目前正在美国政府和商业支持下进入人体临床试验。这项工作表明，PIV作为候选疫苗的应用仍然是针对病原体威胁进行快速有效干预的重要工具。迄今为止，PIV疫苗是使用化学或放射性灭活方法开发的;这两种方法都有严重的缺点。添加灭活化学品，如甲醛，有可能改变抗原靶标的构象结构并损害保护性表位的识别。疫苗生产过程中使用的有害化学品在用于临床试验之前也需要严格清除，这给疫苗开发增加了额外的加工、成本和监管问题。虽然伽马辐照消除了化学干预的需要，但它在需要放射性同位素进行操作的技术方面具有严重的局限性。X射线辐照为PIV疫苗的生产提供了一种解决方案，因为它消除了使用放射源来产生杀死病原体所需的射线的需要。这是一项新兴技术，具有巨大的潜在利益，包括在发展中国家直接应用更便宜和安全。随着PIV疫苗的好处被最近开发的寨卡病毒疫苗所证明，PHE将使用裂谷热病毒开发一种概念验证方法，用于使用X射线辐照材料来产生候选疫苗。如果成功，这种方法可以用于不同的病毒病原体，并与应对新出现的健康威胁高度相关，因为可以快速应用于可能出现并威胁人类健康的新分离病毒。

Many vaccines that have been successfully used for decades have relied on inactivating pathogenic material to render it uninfectious. One benefit of this approach will be the recipients immune system "seeing" the whole pathogen, so the resultant immunity generated will be primed in preparation for exposure to the live pathogen. Other benefits include immunity being generated across a wide array of antigens, rapid scalability, a known safety profile and cost effectiveness.Purified inactivated virus (PIV) vaccines were recently developed for Zika virus, demonstrating protection in animal models including non-human primates and are now entering human clinical trials with US government and commercial support. This work demonstrates that the application of PIV as vaccine candidates remains an important tool for producing rapid and efficacious interventions against pathogenic threats. To date, PIV vaccines are developed using chemical or radiological methods for inactivation; both of which confer severe disadvantages. Addition of inactivation chemicals, such as formaldehyde, risks altering the conformational structure of antigenic targets and compromising the recognition of protective epitopes. Harmful chemical used during the manufacture of vaccines will also need stringent removal before being used for clinical trials adding extra processing, costs and regulatory issues to vaccine development. Whilst gamma irradiation negates the need for chemical intervention, it has a severe limitation with the technology requiring radioactive isotopes for operation. This has financial, environmental, security and moral impacts associated with the use of radiation.X-ray irradiation offers a solution to the production of PIV vaccines by removing the need for radioactive sources to generate beams required to inactivate pathogens. This is a new and emerging technology with huge potential benefits, including being cheaper and secure for direct applications within developing countries. With the benefits of PIV vaccines being exemplified by the recently developed Zika virus vaccine, PHE would use Rift Valley Fever virus to develop a proof-of-concept approach for the use of x-ray irradiated material to generate vaccine candidates. If successful, this approach could be used across different viral pathogens and be highly relevant for responding to emerging health threats as can be rapidly applied to newly isolated viruses that might emerge and threaten human health.