Serological Vaccine Standards for Emerging Diseases

针对埃博拉和寨卡等新发疾病开发安全、有效和经济上负担得起的疫苗，不仅可以提供强有力的工具，防止这些疾病在流行国家重新出现，还可以迅速和有效地控制受感染的回国旅行者引发的疫情。然而，这些传染性病原体只能在高水平的生物安全下处理，这使得大多数商业组织无法承担研究这些病原体的成本。既定标准和参考材料的可用性加速了获得许可的疫苗的开发。如果有确凿的证据表明恢复期血清（即从传染病康复者身上获得的血清）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品是非常有益的。这些血清标准品可作为血清学保护的体外参考标记物，促进临床前和早期临床开发和选择最有希望的实验性疫苗，而无需在生物控制下进行昂贵的研究。NIBSC是世界卫生组织（世卫组织）为疫苗等生物药品制定国际标准和参考材料的全球领导者。应世卫组织的要求，国家疫苗标准局正在执行一项方案，为世卫组织的《重点病原体清单》制定和建立血清诊断参考材料，该清单与联合王国疫苗网络的《重点新发疾病清单》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月制定。2018年10月将审查抗寨卡病毒抗体标准以及抗中东呼吸综合征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进行了详细的体外分析，但如果没有InnovateUK的额外竞争性资助，就不可能确定血清学参考材料含有能够在体内模型系统中预防感染或疾病的特异性抗体。它们现已确立为血清学疫苗标准，并可在全球范围内使用。之前的创新英国基金（为期1年）使NIBSC能够与波顿唐的Dstl和PHE实验室合作。这些国家的高水平生物防护设施使这些关键的防护研究得以开展，并证明针对埃博拉病毒、寨卡病毒和MersCoV病毒的血清学参考材料可以防范这些致命疾病。在这三个中心之间建立了有效的合作关系之后，NIBSC现在正在寻求进一步的2年资金，以巩固这一势头，利用该平台技术制备另外9种候选血清诊断参考制剂，每种用于剩余的英国疫苗网络优先新兴疾病，并确定这些材料是否可以在适当的体内模型系统中提供保护。如果材料有保护作用，那么它们就会增加血清学疫苗标准清单，从而加速针对基孔肯雅热、刚果出血热、马尔堡、拉沙热、尼帕病毒、汉塔病毒、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.