Development and manufacture of an improved replication-deficient simian adenoviral vector to prevent COVID-19

COVID-19的一种主要候选疫苗是被称为ChAdOx 1 nCoV-19的黑猩猩腺病毒载体，该载体由牛津大学和Vaccitech联合开发，然后独家授权给阿斯利康。该疫苗正在英国的11,000多名参与者中进行评估，主要是作为单一免疫接种，并将于8月在美国开始一项3万人的3期研究。有人担心，这种候选疫苗可能需要第二剂，甚至可能需要每年接种一次，而且随着时间的推移，对载体本身的免疫反应可能会限制ChAdOx 1 nCoV-19的有效性。Vaccitech开发了一种更具免疫原性的大猩猩腺病毒载体，具有更低的载体交叉反应性，诱导更强的免疫应答（抗体和T细胞），并克服了目前对ChAdOx 1 nCoV-19的一些担忧。在本提案中，将完成所有临床前工作，以准备提交监管申请，从而开始初始I期临床研究。该准备包括动物研究、临床试验批次生产、正式毒理学研究和任何必要的监管互动。

A leading candidate vaccine for COVID-19 is the chimpanzee adenoviral vector known as ChAdOx1 nCoV-19, which has been jointly developed and then exclusively licensed by the University of Oxford and Vaccitech to AstraZeneca. The vaccine is being evaluated in over 11,000 participants in the UK primarily as a single immunisation and in August will begin a 30,000-person Phase 3 study in the United States. There are concerns that this candidate vaccine may require a second dose, and may even be needed on a yearly basis, and that immune responses to the vector itself may limit the effectiveness of ChAdOx1 nCoV-19 over time. Vaccitech has developed a more immunogenic gorilla adenoviral vector with potential to have less vector cross-reactivity, induce stronger immune responses (both antibodies and T cells), and overcome some of the present concerns with ChAdOx1 nCoV-19. In this proposal all pre-clinical work will be completed to be ready to file a regulatory application to begin the initial Phase 1 clinical study. This preparation includes animal studies, clinical trial lot manufacture, formal toxicology studies, and any necessary regulatory interactions.