Novel multivalent vaccines against haemorrhagic fevers

最近爆发的埃博拉病毒、中东呼吸综合征和寨卡病毒突出表明，全球缺乏防范和针对已知暴发病原体的可行治疗解决方案。为了准备控制未来的爆发，针对“优先病原体”的候选疫苗，如英国疫苗网络和其他组织所确定的，应该被推进临床开发，并测试安全性、免疫原性，以及在可能的情况下，有效性。为了可行，新的疫苗平台将需要1)随着时间的推移具有免疫效果，2)可可靠部署，以及3)具有成本效益。针对单个病毒单独施用的单价疫苗，对于开发针对所有“重点病原体”的疫苗来说将是非常昂贵的，而且在预防环境中部署起来也很麻烦。在此，我们建议开发有效且具有成本效益的多价疫苗，以对抗非洲流行的几种致死性出血热病毒，包括丝状病毒（埃博拉病毒和马尔堡病毒）和沙粒病毒（拉沙病毒）。多价疫苗将使开发和生产费用大大减少，并将增加获得针对大多数而不是少数病原体的疫苗的可能性。我们预先开发的核心疫苗平台（病毒载体）已被证明能够表达多种抗原，并在其他传染病环境中诱导持久的免疫反应。对于我们开发的针对爆发病原体的每一种多价疫苗，将进行临床前测试，以确定能够诱导“同类最佳”免疫反应并最适合临床生产和现场使用的疫苗。通过评估两种不同病毒载体平台中不同抗原的几种组合，我们将优化开发既适合预防又适合疫情应对环境的疫苗接种方案的机会。在这项工作结束时，我们将开发、测试和生产pre-GMP库存，作为可扩展的疫苗解决方案，用于部署针对丝状病毒和沙粒病毒的疫苗，并将开发可扩展的平台模式，可用于其他爆发场景。

Recent outbreaks of Ebola, MERS and Zika viruses have highlighted the lack of global preparedness and viable therapeutic solutions for known outbreak pathogens. To prepare for the control of future outbreaks, vaccine candidates against 'priority pathogens', as identified by the UK vaccines network and other organisations, should be taken forward into clinical development and tested for safety, immunogenicity and, wherever possible, efficacy. To be viable, new vaccine platforms will need to be 1) immunologically effective over time, 2) reliably deployable, and 3) cost effective. Monovalent vaccines, administered singularly against individual viruses, will be prohibitively expensive to develop for all ‘priority pathogens’ and burdensome to deploy in the prophylactic setting. Here, we propose to develop efficacious and cost-effective multivalent vaccines against several lethal haemorrhagic fever-causing viruses endemic in Africa, including Filoviruseses (Ebolaviruses & Marburg virus) and Arenaviruses (Lassa virus). Multivalent vaccines will allow the development and production outlays to be greatly reduced, and will increase the probability that vaccines against most, rather than a select few, pathogens will be available. Our pre-developed core vaccine platforms (viral vectors) have proven capability of expressing multiple antigens and inducing durable immune responses in other infectious disease settings. For each of the multivalent vaccines against outbreak pathogens that we develop, preclinical testing will be conducted to identify the vaccines which induce ‘best–in-class’ immune responses and are most suitable for clinical manufacture (GMP) and field use. By assessing several combinations of different antigens in two different viral vector platforms, we will optimise the chances of developing vaccination regimens suitable for both prophylactic and outbreak response settings. At the end of this work, we will have developed, tested and produced pre-GMP stocks as scalable vaccine solutions for deployment against Filoviruses and an Arenavirus and will have developed scalable platform modalities that can be used in other outbreak scenarios.