Ebola vaccines: persistence of immunity & response to booster dose of MVA-EBO Z

最近在西非爆发的埃博拉病毒导致了一场史无前例的全球努力，以开发针对这种致命病毒的疫苗，最终直接证明了其中一种候选疫苗的有效性。这一证据表明，免疫接种可以预防埃博拉病毒感染，这表明它们将在控制未来埃博拉病毒疾病爆发方面发挥关键作用。使用这些疫苗的一个潜在方法是对疾病风险增加的人群进行先发制人的免疫接种，包括卫生保健工作者(居住在高危地区或作为国际应对小组的一部分)。当以这种方式使用时，疫苗诱导免疫的持久性对于确保针对疫情的长期保护至关重要，疫情爆发的时间本身就无法预测。因此，在这个项目中，我们将提供世界上第一个关于免疫后免疫持久性的数据，时间表包括四个领先的埃博拉候选疫苗。这些疫苗包括牛津大学开发的MVA-EBO Z疫苗，在与其他埃博拉疫苗免疫后，它在“提高”免疫力方面具有特殊作用。此外，还将评估后期接种MVA-EBO Z疫苗的免疫应答，以及接种后1年这种应答的持久性。为了实现这一目标，在英国和塞内加尔完成6期1期和2期埃博拉疫苗研究的所有394名参与者将被邀请参加这些后续研究，在首次免疫后2至3年进行血液测试。除一项研究外，所有这些研究的参与者都将接受增强剂量的MVA-EBO Z，其余的一组(约35名参与者)作为非强化“对照”。接种后一个月将进行血液测试，所有参与者在注册一年后再进行血液测试。抗体和细胞免疫反应将在牛津和塞内加尔的实验室进行评估。牛津的疫苗试验单位特别适合进行这些研究，在最近的疫情爆发期间，他们对非洲测试的五种疫苗中的四种进行了“人类第一次”剂量的接种。该方案将提供有关免疫持久性的新数据，这对于全球社会了解如何最好地部署这些疫苗以减少这种毁灭性疾病的未来暴发至关重要。

The recent Ebola virus outbreak in West Africa resulted in an unprecedented global effort to develop vaccines against this deadly virus, culminating in direct evidence for efficacy for one of the candidate vaccines. This proof that immunisations can protect against Ebola virus infection suggests that they will have a crucial role in the control of future outbreaks of Ebola virus disease.One potential approach to use of these vaccines is pre-emptive immunisation of populations at increased risk of disease, including health care workers (either resident in at-risk areas or as part of international response teams). When used in this way the persistence of vaccine induced immunity is of critical importance to ensure long-term protection against outbreaks, the timing of which are inherently unpredictable.Accordingly in this project we will provide world first data on the persistence of immunity following immunisation with schedules including four of the leading Ebola vaccine candidates. These include MVA-EBO Z, a vaccine developed in Oxford that has a particular role in ‘boosting’ immunity following immunisation with other Ebola vaccines. Furthermore, the immune response to a late booster dose of the MVA-EBO Z vaccine will be evaluated, as will the persistence of this response to 1 year after boosting.To achieve this all 394 participants completing the six phase 1 and 2 Ebola vaccine studies in the UK and Senegal will be invited to participate in these ‘follow-on’ studies, in which blood tests will be taken at 2 to 3 years after initial immunisation. Participants in all but one of these studies will receive a booster dose of MVA-EBO Z, with the remaining group (approximately 35 participants) acting as non-boosted ‘controls’. Blood tests will be taken one month after boosting, with all participants having a further blood test at one year after enrolment. Antibody and cellular immune response will be evaluated at laboratories in Oxford and Senegal.The vaccine trial units at Oxford are particularly well placed to conduct these studies, having administered the ‘first in human’ dose for four of the five vaccines tested in Africa during the recent outbreak. This programme will providing novel data on immune persistence that is essential to the global community’s understanding of how these vaccines can be best deployed to curtail future outbreaks of this devastating illness.