GMP Manufacture of a vaccine targeting a viral hemorrhagic fever

马尔堡病毒病与埃博拉病毒引起的疾病难以区分，并且与高病死率相关。马尔堡病毒主要在东非和中非引起疾病暴发，1975年至2021年期间记录了11起暴发事件。最近一次马尔堡病毒爆发的地点引起了对病毒传播到西非的关切，因为以前的爆发仅限于肯尼亚、乌干达和刚果民主共和国。马尔堡病毒是一种具有大流行性和流行潜力的病毒，目前临床上还没有疫苗可以预防由马尔堡病毒引起的疾病。我们选择的疫苗模式，用于疫苗生产，是黑猩猩腺病毒载体（ChAdOx 1）。ChAdOx 1方案具有高度免疫原性，我们已经证明它们可以诱导对疾病的保护（例如Oxford/AstraZeneca ChAdOx 1 nCOV-19可以预防COVID-19）。值得注意的是，针对COVID-19的紧急应对措施已导致该疫苗技术的大规模生产，目前已积累了大规模生产疫苗的经验，且价格可用于低收入和中等收入国家。我们已经开始生产一种针对马尔堡病毒的疫苗，在这项申请中，我们将通过GMP（良好生产规范）生产这种疫苗-生产一种可用于人类预防病毒性出血性疾病的疫苗。我们现在希望对ChAdOx 1马尔堡进行研究，以允许ChAdOx 1-马尔堡疫苗的发布，鉴于马尔堡病毒在赤道几内亚和坦桑尼亚的爆发以及世卫组织优先委员会对ChAdOx 1-马尔堡疫苗的选择，这是至关重要的。

Marburg virus disease is indistinguishable from disease caused by Ebolaviruses and is associated with a high case fatality rate. Marburg virus has caused disease outbreaks predominantly in Eastern and Central Africa, with eleven incidences of outbreaks on record between 1975 and 2021\. The location of the most recent Marburg virus outbreak has caused concern regarding viral spread into Western Africa as previous outbreaks have been limited to Kenya, Uganda and the Democratic Republic of the Congo. Marburg virus has been identified as a virus of pandemic and epidemic potential.There are no clinically available vaccines that can protect against disease caused by Marburg virus. Our vaccine modality of choice, for vaccine manufacture, is a chimpanzee adenoviral vector (ChAdOx1). ChAdOx1 regimens are highly immunogenic, and we have demonstrated they can induce protection against disease (e.g. the Oxford/AstraZeneca ChAdOx1 nCOV-19 protects against COVID-19). Of note, the emergency response against COVID-19 has led to large-scale manufacture of this vaccine technology and there is now an accumulated manufacturing experience to generate vaccines at scale and at a price which can be used in low and middle income countries. We have started to generate a vaccine against Marburg virus and in this application we will progress this vaccine through GMP (Good Manufacturing Practice) production - generating a vaccine that can be used in humans to protect against viral haemorrhagic disease. We now wish to progress the ChAdOx1 Marburg to allow for release of the ChAdOx1-Marburg vaccine which is of utmost importance given the outbreak of Marburg virus in Equatorial Guinea and Tanzania and the selection of ChAdOx1-Marburg vaccine by the WHO prioritization committee.