Clinical development of the new ChAdOx1 Plague vaccine: A Phase 1b trial in a target population

该项目的目的是通过在乌干达进行临床试验，推动一种有前景的鼠疫疫苗的临床开发。鼠疫引起的黑死病夺去了欧洲50%的人的生命，而且鼠疫非但没有灭绝，在世界上的一些国家仍在反复流行和暴发。尽管自1890年以来，有时使用基于杀死细菌的鼠疫疫苗对当地人群和旅行者进行免疫接种，但没有足够的证据证明其有效性，而且当地的吸收情况也各不相同。基于佐剂中的蛋白质的传统疫苗已经开发出来，并在动物模型中显示出一定程度的保护，但它们需要注射两到三次。这严重限制了它们在流行和暴发环境中的有用性。这种疾病影响着穷人中的穷人，他们生活在基础设施匮乏的偏远地区。对于像马达加斯加这样每年受影响最严重的国家来说，三剂疫苗计划成本太高，后勤也很困难。在疫情爆发期间，需要每隔一个月注射三剂的疫苗用途有限，而第一剂基于腺病毒的疫苗能够诱导抗体的保护水平，例如针对埃博拉病毒和COVID-19的抗体，可以通过第二剂进一步增强和维持。因此，为了应对鼠疫造成的持续公共卫生威胁，我们基于使用腺病毒的最先进疫苗递送技术，开发了一种针对这一古老而令人恐惧的疾病的疫苗，该技术与牛津/阿斯利康针对COVID-19的疫苗使用的平台相同。由此产生的基于病毒载体的疫苗是安全的，并诱导产生高质量的免疫反应。该疫苗在相关动物模型中显示出前所未有的潜力，甚至可以通过单次注射预防最致命的鼠疫（肺鼠疫）。因此，这种疫苗有可能大大减少鼠疫的发病率和相关影响，如贫困。临床开发已经开始，目前正在牛津进行第一阶段人体试验，以证明疫苗在人体中的安全性。临床开发的下一步是证明疫苗在目标人群中也是安全的和具有免疫原性的，在这个项目中，我们建议在乌干达与一个在现场进行临床试验方面有丰富经验的合作伙伴进行这项试验。[] [0] [0]: applewebdata: / / 64259500 - 5 - eda - 47 - b8 - b70b e2e3713e69d1 # _msoanchor_1

The aim of this project is to progress the clinical development of a promising plague vaccine by conducting a clinical trial in Uganda. Plague caused the Black Death that killed 50% of Europe, and far from being extinct, recurrent plague epidemics and outbreaks still occur in several countries in the world. The need for a new vaccine against this disease is urgent Although plague vaccines based on killed bacteria have been sometimes used to immunize local populations and travellers since 1890, there has been insufficient proof of efficacy and local uptake has varied. Conventional vaccines based on proteins in adjuvant have been developed and demonstrated a certain degree of protection in animal models, but they necessitate two to three injections. This is seriously limiting their usefulness for both the endemic and the outbreak settings. This disease affects the poorest of the poor, living in remote area with little infrastructure. A 3-doses vaccine program would be too costly and logistically difficult for the countries most affected every year like Madagascar. During an outbreak, a vaccine that requires three doses at a month interval is of limited use, while a first dose of an adenovirus-based vaccine is able to induce protective levels of antibodies for example against Ebola and COVID-19, that can be further boosted and maintained by a second dose. In response to the ongoing public health threat posed by plague, we have thus created a vaccine against this ancient and feared disease, based on this state-of-the-art vaccine delivery technology using an adenovirus, the same platform used for the Oxford/ Astra Zeneca vaccine against COVID-19\. The resulting viral vectored- based vaccine is safe and induces the production of high-quality immune responses. The vaccine has demonstrated an unprecedented potential to prevent even the deadliest form of plague (pneumonic), using a single injection, in the relevant animal model. Therefore, this vaccine has the potential to substantially reduce the morbidity of plague and associated impacts such as poverty. The clinical development has already started with a first-in-man phase 1 trial, currently ongoing in Oxford, to demonstrate the vaccine's safety in humans. The next step in the clinical development is to demonstrate that the vaccine is also safe and immunogenic in a target population, and in this project we propose to conduct this trial in Uganda, with a partner that has a solid experience in conducting clinical trials on site.[][0][0]: applewebdata://64259500-5EDA-47B8-B70B-E2E3713E69D1#_msoanchor_1