Novel multivalent vaccines against haemorrhagic fevers

最近埃博拉、中东呼吸综合征和寨卡病毒的爆发凸显了全球缺乏对已知爆发病原体的准备和可行的治疗方案。为准备控制未来的疫情，应将针对英国疫苗网络和其他组织确定的“优先病原体”的候选疫苗推向临床开发，并进行安全性、免疫原性和有效性（如可能）测试。为了可行，新的疫苗平台将需要1）随着时间的推移免疫有效，2）可靠的部署，和3）成本效益。单价疫苗，针对单个病毒单独给药，将是非常昂贵的开发所有的“优先病原体”和繁重的部署在预防性设置。在这里，我们建议开发有效的和具有成本效益的多价疫苗，对几个致命的出血热引起的病毒在非洲流行，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，并将增加针对大多数而不是少数几种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应答。对于我们开发的每种针对爆发病原体的多价疫苗，将进行临床前测试，以确定诱导“同类最佳”免疫应答的疫苗，并且最适合临床生产（GMP）和现场使用。通过评估两种不同病毒载体平台中不同抗原的几种组合，我们将优化开发适用于预防和爆发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GMP前库存，作为可扩展的疫苗解决方案，用于部署对抗丝状病毒和沙粒病毒，并将开发可用于其他爆发情况的可扩展平台模式。

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.