EML-VAC: Multivalent replicon vaccine against Ebola, Marburg and Lassa viruses

EML-VAC：针对埃博拉、马尔堡和拉沙病毒的多价复制子疫苗

• 批准号: 971617
• 金额: $ 345.02万
• 依托单位: IMPERIAL COLLEGE LONDON
• 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=971617
• 关键词: EML; VAC; Multivalent; replicon; vaccine

A multivalent haemorrhagic fever vaccine based on synthetic replicating ribonucleic acid would provide one of the fastest and most cost-effective approaches to stop viral outbreaks at their source. This affords significant advantages over more conventional vaccine approaches such as viral vectors, and attenuated pathogens and would be safer in individuals unable to receive live attenuated vaccines (e.g. children and the immunocompromised ). Our program aims to develop a multivalent vaccine against the most common human viral haemorrhagic fevers ( Ebola, Marburg and Lassa fever virus). The choice of targets is based on strong scientific evidence that gene-based approaches can protect against infection in preclinical models. This vaccine may also find utility as a booster that can be used in combination with existing vaccines (e.g. rVSV-EBOV). The fully synthetic manufacture and ease of production provides the potential to produce hundreds of thousands of doses within a matter of weeks where the individual vaccine components targeting different haemorrhagic viruses can easily be combined. This may be critical to the global response against emerging haemorrhagic viral infections, as the nature of the next outbreak cannot be reliably predicted. In this respect the proposed multivalent vaccine has potential not only to protect against multiple known haemorrhagic viruses but is also more likely to show cross-protection against novel variants that may arise in the future. In Part 1 of this project (now complete) we successfully completed the heavy lifting required to move our RNA platform from a research process through to fully established robust and validated manufacturing process, confirming the potency of the produced product in preclinical models. In this Part 2 project we will manufacture clinical grade material (GMP), conduct the required preclinical toxicology and early evaluation of the vaccine in a phase I human clinical trial designed to assess the safety and immunogenicity of our pan-haemorrhagic fever vaccine. Our ability to deliver on the aggressive timelines required to move from manufacture through to completion of a first in human clinical trial within two-year grant funding period is only possible due to the robustness and speed of our manufacturing process and the unique competency of the assembled team in translating vaccine concepts from the bench to the bedside . Ultimately our vision is to use our vaccine platform to ensure UK preparedness for any eventual pandemic and to make vaccines globally available in the event of any outbreak situation. Our approach will ensure appropriate costing for low and middle-income countries and be readily available to organizations focused on global health (e.g. MSF and WHO): these groups have historically been the first to detect, and/or respond to an outbreak, and are therefore ideally positioned to assist in implementing any vaccination strategy. Our Target Product Profile (TPP) is a stable multivalent vaccine that can elicit protective immunity against the most common human viral haemorrhagic fevers following one or two immunisation across all populations, has potential for boosting in the absence of anti-vector immunity, and can be rapidly manufactured at low cost.

基于合成复制的核糖核酸的多价出血热疫苗将提供最快，最具成本效益的方法之一，以阻止其来源的病毒爆发。这比传统的疫苗方法（例如病毒载体）具有很大的优势，并减弱了病原体，并且在无法接收活衰减的疫苗（例如儿童和免疫功能低下）的个体中会更安全。我们的计划旨在开发针对最常见的人类病毒出血发烧的多价疫苗（Ebola，Marburg和Lassa Fever病毒）。目标的选择基于有力的科学证据，即基于基因的方法可以预防临床前模型中的感染。该疫苗还可以找到可以与现有疫苗（例如RVSV-EBOV）结合使用的助推器。完全合成的生产和易生产性提供了在几周内产生数十万剂剂量的潜力，即单个疫苗成分靶向不同的出血病毒。这对于全球反应对新出现的出血病毒感染的反应至关重要，因为下次爆发的性质无法可靠地预测。在这方面，拟议的多价疫苗不仅具有预防多种已知的出血病毒的潜力，而且更有可能在未来可能出现的新型变体中表现出交叉保护。在该项目的第1部分（现已完成）中，我们成功地完成了将RNA平台从研究过程转移到完全建立的健壮且经过验证的制造过程所需的繁重举重，从而证实了临床前模型中生产产品的效力。在本第2部分项目中，我们将制造临床级材料（GMP），在I期人类临床试验中进行所需的临床前毒理学和对疫苗的早期评估，旨在评估泛 - 释放发烧疫苗的安全性和免疫原性。我们能够在两年的赠款资金期内从制造到完成人类临床试验的首次迁移到完成的攻击性时间表的能力，这是由于我们制造过程的稳健性和速度以及组装团队在将疫苗从床头转换为床边的独特能力。最终，我们的愿景是利用我们的疫苗平台来确保英国为任何最终的大流行准备，并在任何爆发情况下全球可用的疫苗可用。我们的方法将确保对低收入和中等收入国家的适当成本，并为关注全球健康的组织（例如MSF和谁）提供适当的成本：这些群体历史上是第一个检测和/或对爆发的反应，因此在理想情况下有助于实施任何疫苗接种策略。我们的目标产品概况（TPP）是一种稳定的多价疫苗，可以在所有种群中进行一次或两种免疫接种后，对最常见的人类病毒流血发烧的保护性免疫，在没有抗媒介免疫力的情况下具有促进的潜力，并且可以低成本以低成本生产。