IMPROVED Q FEVER VACCINE (DSTL, PHE, ICENI DX & MOLOGIC)

该项目通过开发基于病毒样颗粒（VLP）的平台技术来提供针对Q Fever的疫苗，以满足全球流行病对新疫苗的需求。Q热的病原体贝氏柯克斯体已被确定为令人关注的病原体，因为其感染剂量低，该生物体能够在环境中长时间存活，并在人类和动物中引起重大暴发。世界范围内，每年都有人类和动物发生Q热疫情。急性感染C.贝氏症通常是一种自限性发热性疾病，常伴有严重头痛，严重者会出现非典型肺炎。慢性疾病，通常表现为心内膜炎，发生在大约5%的病例中，如果不治疗通常是致命的。VLP由组装形成病毒结构（如衣壳或包膜）的蛋白质形成，VLP模拟入侵病毒，但由于其不包含必要的遗传密码而无法感染并引起感染。当用于免疫时，VLP被识别为外来因子，并且颗粒表面上抗原的密集排列引起强烈的免疫应答。Mologic已经开发了一种B型肝炎病毒核心VLP的衍生物，其允许将不相关的抗原（例如来自其他病毒或细菌的抗原）附着到颗粒的表面，使得它们以与完整病毒相同的免疫原性特征展示给免疫系统。SBRI资助的“全球流行病新疫苗：开发和生产”项目，使该VLP技术得以进一步利用Q热病原体（贝氏柯克斯体）作为靶标，并使该项目能够与Dstl、PHE和Iceni Diagnostics的专家合作，没有他们，该项目就不可行。该财团现在希望进一步开发技术，以测试候选疫苗对抗贝氏柯克斯体攻击的有效性。这将使我们能够确定最有效的候选产品，用于扩大生产和进一步研究，以确定最佳配方和剂量。第二阶段研究将资助疫苗平台的开发，使其准备好进行商业化，生产和GLP临床前测试。

This project addresses the need for new vaccines for global epidemics by the development of a virus-like particle (VLP) based platform technology to deliver a vaccine against Q Fever. The causal agent of Q fever, Coxiella burnetii has been identified as an agent of concern due to its low infectious dose, the ability of the organism to survive for long periods in the environment and cause significant outbreaks in both humans and animals. Outbreaks of Q fever are recorded in humans and animals on an annual basis, worldwide. Acute infection with C. burnetii usually presents as a self-limiting febrile illness often accompanied by severe headaches and in severe cases atypical pneumonia occurs. Chronic disease, typically presenting as endocarditis, occurs in approximately 5 % of cases and without treatment is usually fatal. Formed of the proteins that assemble to form the viral structure such as the capsid or envelope, a VLP mimics an invading virus but is unable to infect and cause infection as it does not contain the necessary genetic code. When used for immunisation, VLPs are recognised as foreign agents and the densely packed arrangement of antigens on the surface of the particles elicits a strong immune response. Mologic have developed a derivative of the Hepatitis B virus core VLP which allows the attachment of unrelated antigens, for example from other viruses or bacteria, to the surface of the particle such that they are displayed to the immune system with the same immunogenic characteristics as a whole virus. The SBRI funding “New vaccines for global epidemics: development and manufacture” has allowed further exploitation of this VLP technology using the causal agent of Q Fever (Coxiella burnetii) as a target and enabled collaboration with experts from Dstl, PHE and Iceni Diagnostics, without whom the project would not have been feasible. The consortium now wish to further develop the technology to test the efficacy of candidate vaccines against challenge with Coxiella burnetii. This will allow us to identify the most effective candidates for scaled up production and further studies to determine optimal formulations and dosage. The phase 2 study will fund the development of the vaccine platform to a stage that it is ready for commercialisation, manufacture and GLP pre-clinical testing.