Serological Vaccine Standards for Emerging Diseases

开发针对埃博拉和寨卡病毒等新出现疾病的安全、有效和经济实惠的疫苗，将提供强有力的工具，不仅可以防止这些疾病在地方性疾病流行的国家再次出现，而且还能够迅速和有效地控制由受感染的回国旅行者引发的疫情。然而，这些感染性物质只能在高度生物安全的情况下处理，这使得对这些物质的研究成本对大多数商业组织来说是令人望而却步的。已建立的标准和参考材料的可获得性加速了许可疫苗的开发。如果有强有力的证据表明恢复期血清(即从传染病恢复者那里获得的血清)可以防止再次感染，那么制备和分发已被证明具有预防感染作用的血清标准是非常有益的。这些血清标准有助于临床前和早期临床开发和选择最有希望的实验性疫苗，而不需要在生物遏制下进行昂贵的研究，因为血清标准提供了作为血清学保护的体外参考标记物。NIBSC在制定世界卫生组织(WHO)建立的疫苗等生物药物国际标准和参考材料方面处于全球领先地位。应世界卫生组织的要求，NIBSC正在开展一项计划，为世界卫生组织的优先病原体清单开发和建立血清诊断参考材料，该清单与英国疫苗网络优先新兴疾病严重重叠。NIBSC制定了抗埃博拉病毒抗体国际标准，该标准由世卫组织生物标准化专家委员会于2017年10月建立。2018年10月将审查抗寨卡病毒抗体标准，以及关于抗MERS冠状病毒抗体材料的初步报告。虽然这些候选材料已经在国际合作研究中通过了详细的体外分析，但如果没有InnovateUK提供的额外竞争性资助，就不可能确定血清参考材料包含能够在体内模型系统中预防感染或疾病的特定抗体。它们现在被确立为血清学疫苗标准，并在全球范围内可用。之前的Innovate UK基金(为期1年)使NIBSC能够与位于Porton Down的DSTL和PHE实验室合作。他们的高水平生物遏制设施使这些关键的保护研究得以进行，并证明了针对埃博拉、寨卡和MersCoV的血清学参考材料可以预防这些致命疾病。在三个中心之间建立了有效的合作之后，NIBSC现在正在寻求另外两年的资金，以巩固这一势头，利用这一平台技术制备另外9种候选血清诊断参考制剂，分别用于剩余的英国疫苗网络优先新兴疾病，并建立这些材料是否可以在适当的体内模型系统中保护作用。如果材料具有保护作用，那么它们将被添加到血清学疫苗标准清单中，从而加速针对基孔肯雅热、CCHF、马尔堡、拉沙热、尼帕、汉塔、裂谷热病毒和细菌感染Q热和鼠疫的疫苗开发。

The development of safe, effective and economically affordable vaccines against Emerging Diseases, such as Ebola and Zika, would provide powerful tools not only to prevent re-emergence of these diseases in countries where they are endemic, but also enable swift and effective control of outbreaks initiated by infected returning travellers. However, these infectious agents can only be handled under high levels of bio-security, making the cost of research on these agents prohibitive for most commercial organisations. The availability of established standards and reference materials accelerates the development of licenced vaccines. Where there is robust evidence that convalescent serum (ie serum obtained from someone who has recovered from an infectious disease) protects against reinfection, then the preparation and distribution of serum standards that have been demonstrated to confer protection against infection is hugely beneficial. These serum standards facilitate pre-clinical and early clinical development and selection of the most promising experimental vaccine without the need for expensive studies under bio-containment, as the serum standard provides as in vitro reference marker for serological protection. NIBSC is the global leader in the development of World Health Organisation (WHO) established International Standards and reference materials for biological medicines such as vaccines. At the request of the WHO, NIBSC is undertaking a programme to develop and establish sero-diagnostic reference materials for the WHO's List of Priority Pathogens,that heavily overlaps with the UK Vaccine Network Priority Emerging Diseases. NIBSC has prepared an International Standard for anti-Ebola virus antibodies that was established by the WHO's Expert Committee for Biological Standardisation in October 2017. An anti-Zika virus antibody standard will be reviewed in October 2018 as well as a preliminary report about an anti-MERS-CoV antibody material. Whilst these candidate materials have been through detailed in vitro analyses in international collaborative studies, without additional competitively awarded funding from InnovateUK, it would not have been possible to establish that the serological reference materials contained specific antibodies capable of preventing infection or disease in in vivo model systems. They are now established as serological vaccine standards and available globally. This previous Innovate UK funding, (for 1 year) enabled NIBSC to collaborate with Dstl and PHE laboratories at Porton Down. Their high level bio-containment facilities allowed these critical protection studies to be performed and demonstrated that serological reference materials against Ebola, Zika and MersCoV could protect against these lethal diseases. Having established an effective collaboration between the 3 centres, NIBSC is now seeking a further 2 years funding to build on this momentum, utilising this PLATFORM TECHNOLOGY to prepare a further 9 candidate sero-diagnostic reference preparations, one each for the remaining UK Vaccine Network Priority Emerging Diseases, and establish whether these materials can protect in appropriate in vivo model systems. If materials protect, then they add to the list of serological vaccine standards and thus accelerate vaccine development against Chikungunya, CCHF, Marburg, Lassa Fever, Nipah, Hanta, Rift Valley Fever viruses and bacterial infections Q Fever and Plague.