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

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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