Clinical trial of a DIOS Trivalent Haemorrhagic Fever Vaccine (DIOS-HFVac3)

DIOS 三价出血热疫苗 (DIOS-HFVac3) 的临床试验

• 批准号: 971616
• 金额: $ 299.43万
• 依托单位: UNIVERSITY OF CAMBRIDGE
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=971616
• 关键词: Clinical; trial; DIOS; Trivalent; Haemorrhagic

Bringing together cutting edge technologies, we have generated a new vaccine candidate that protects against 3 highly contagious African Haemorrhagic Fever Viruses (HFV), which have significant global epidemic potential. With this technology, we can achieve dramatic improvements to the breadth of protection conferred by vaccines against emerging and re-emerging pathogens. Our DIOS (Digitally designed, Immune Optimised and Selected) technology provides the broadest possible protection against viral variants to limit future outbreaks of highly variable pathogens. In our Innovate Stage 1 project, we achieved clear proof-of-concept for this platform, moving quickly from demonstrating DIOS platform immunogenicity to generate a unique trivalent vaccine candidate. In a second Stage 1 project, animals vaccinated against three diverse viruses - Lassa, Ebola and Marburg were protected from lethal infection. Our top candidate next generation DIOS antigens, targeting these 3 diverse families of HFVs, gave the broadest immune responses and proved stable in the MVA vaccine vector. In the Innovate Stage 2 project we propose to take this to next stage, performing a “first-in-human” clinical trial of DIOS vaccine inserts to demonstrate the safety profile of the DIOS-HFVac3 candidate and its improved breadth of the immune responses in human volunteers. We have proven that DIOS inserts based on both the DNA vaccine vector pEVAC and the highly immunogenic poxvirus vaccine vector, Modified Vaccinia Ankara (MVA), provide protection from infection. MVA is a safe vector that was used to successfully immunise against smallpox. It is well characterised and has further been modified as a versatile vaccine vector for many pathogens. MVA additionally provides 100% vaccine efficacy against Monkeypox, a disease which is currently causing outbreaks in humans in the same regions where DIOS-HFVac3 would be deployed as a vaccine. It has been demonstrated that cold chain independent vaccine lots of MVA can be produced and we would aim to achieve this with both the pEVAC and MVA DIOS inserts for rapid deployment wherever outbreaks may occur. Our human clinical trial design will have two arms, one with MVA/DIOS-HFVac3 alone, and the other with co-administration of MVA expressing a fourth HFV found in Africa, namely Crimean-Congo Haemorrhagic fever virus (CCHFV). In collaboration with the MVA-CCHF Innovate clinical trial consortium, GMP lots of MVA-CCHF, made to the same standards as MVA-DIOS-HFVac3, will be used for co-administration. This represents a unique opportunity to evaluate if a tetravalent human VHF vaccine will provide equivalent immunogenicity, and potentially protect humans against 4 VHF pathogens (Lassa, Ebola, Marburg, CCHF) as well as Monkeypox. 5. Description of Proposed Idea/Technology

结合尖端技术，我们产生了一种新的候选疫苗，可以预防3种具有重大全球流行潜力的高度传染性的非洲出血热病毒(HFV)。有了这项技术，我们可以大幅改善疫苗对新出现和再次出现的病原体的保护范围。我们的DIOS(数字设计、免疫优化和精选)技术提供最广泛的保护，防止病毒变异，以限制未来高度可变病原体的爆发。在我们的创新阶段1项目中，我们为该平台实现了明确的概念验证，从演示Dios平台的免疫原性快速发展到产生独特的三价候选疫苗。在第二阶段1项目中，对三种不同病毒--拉萨病毒、埃博拉病毒和马尔堡病毒--接种疫苗的动物受到保护，不会受到致命感染。我们的首选下一代Dios抗原针对这3个不同的HFV家族，提供了最广泛的免疫反应，并被证明在MVA疫苗载体中是稳定的。在创新阶段2项目中，我们建议将这一点带入下一阶段，对插入的Dios疫苗进行“人类首例”临床试验，以展示Dios-HFVac3候选疫苗的安全性及其在人类志愿者中改善的免疫反应广度。我们已经证明，基于DNA疫苗载体pEVAC和高度免疫原性的痘病毒疫苗载体改良的Vaccinia Ankara(MVA)的DIOS插入片段可提供免受感染的保护。MVA是一种安全的媒介，曾被用来成功地免疫天花。它具有很好的特性，并已被进一步修改为多种病原体的通用疫苗载体。此外，MVA还为猴痘提供100%的疫苗效力。猴痘是一种疾病，目前正在Dios-HFVac3作为疫苗部署的同一地区的人类中引起疫情。已经证明，冷链非依赖疫苗可以生产大量MVA，我们的目标是通过插入pEVAC和MVA Dios来实现这一目标，以便在任何可能发生疫情的地方快速部署。我们的人类临床试验设计将有两个手臂，一个单独使用MVA/Dios-HFVac3，另一个联合注射MVA，表达在非洲发现的第四种HFV，即克里米亚-刚果出血热病毒(CCHFV)。在与MVA-CCHF创新临床试验联盟的合作下，GMP许多MVA-CCHF将用于联合给药，这些MVA-CCHF与MVA-Dios-HFVac3的标准相同。这是一个独特的机会，可以评估四价人用VHF疫苗是否能提供同等的免疫原性，并潜在地保护人类免受4种VHF病原体(拉沙氏、埃博拉、马尔堡、CCHF)和猴痘的侵袭。5.建议构思/技术的描述