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

基于合成复制核糖核酸（RepRNA）的多价出血热疫苗将提供最快和最具成本效益的方法之一，从源头上阻止病毒爆发。这提供了比更常规的疫苗方法（例如病毒载体和减毒病原体）更显著的优点，并且在不能接受活减毒疫苗的个体（例如儿童和免疫功能低下者）中更安全。该疫苗也可用作可与现有疫苗（例如rVSV-EBOV）组合使用的加强剂。全合成制造和易于生产提供了在几周内生产数十万剂的潜力，其中针对不同出血性病毒的单独疫苗组分可以容易地组合。这可能对全球应对新出现的出血性病毒感染至关重要，因为无法可靠地预测下一次疫情的性质。在这方面，所提出的多价疫苗不仅有可能针对多种已知的出血性病毒提供保护，而且更有可能针对可能出现的新变体显示交叉保护。拟议的疫苗可以有效地冷冻干燥，提供一种便携和稳定的产品，可以承受温度波动，而不需要冷链。该计划旨在开发针对最常见的人类病毒性出血热（两种埃博拉病毒，马尔堡病毒和拉沙病毒）的多价疫苗。靶点的选择基于强有力的科学证据，即基于基因的方法可以在临床前模型中保护免受感染。第1部分项目将支持疫苗表征、概念验证“体内”研究和工艺最终确定，以便在项目完成后，一切都将到位，以便在第2部分成功资助后迅速进入早期I期人体试验。我们的愿景是确保低收入和中等收入国家的适当成本，并使专注于全球卫生的组织（例如无国界医生组织和世卫组织）随时可以获得疫苗，因为这些组织历来是最先发现和/或应对疫情的组织，因此处于协助实施任何疫苗接种策略的理想位置。我们的目标产品概况（TPP）是一种温度稳定的多价疫苗，在所有人群（成人、儿童和免疫功能低下者）中进行单次免疫接种后，可引发针对最常见的人类病毒性出血热的保护性免疫，在缺乏抗载体免疫的情况下具有加强免疫的潜力，并且可以低成本快速生产。

A multivalent hemorrhagic fever vaccine based on synthetic replicating ribonucleic acid (RepRNA) 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). 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 hemorrhagic viruses can easily be combined. This may be critical to the global response against emerging hemorrhagic 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 hemorrhagic viruses but is also more likely to show cross-protection against novel variants that may arise. The proposed vaccine can be effectively freeze-dried providing a portable and stable product that can withstand temperature oscillations without the requirement for a cold chain. The program aims to develop a multivalent vaccine against the most common human viral hemorrhagic fevers (two Ebola viruses, Marburg virus and Lassa virus). The choice of targets is based on strong scientific evidence that gene based approaches can protect against infection in preclinical models. This Part 1 project will support vaccine characterisation, proof of concept ‘in vivo’ studies and process finalisation, such that on completion of the project everything will be in place to rapidly move into early phase I human trials upon successful Part 2 funding. Our vision is to ensure appropriate costing for low and middle income countries and to make the vaccine readily available to organizations focused on global health (e.g. MSF and WHO), as 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 temperature stable multivalent vaccine that can elicit protective immunity against the most common human viral hemorrhagic fevers following a single immunisation across all populations (adults, children and the immunocompromised), has potential for boosting in the absence of anti-vector immunity, and can be rapidly manufactured at low cost.