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热的疫苗，解决了对全球流行病新疫苗的需求。Q热的致病因子伯纳蒂克希菌已被确定为一种令人关注的病原体，因为它的感染剂量低，该生物能够在环境中长时间生存，并在人类和动物中引起重大暴发。全世界每年都有在人类和动物中爆发Q热的记录。伯纳蒂胞杆菌急性感染通常表现为一种自限性发热性疾病，常伴有严重头痛，严重者可发生非典型肺炎。慢性疾病，通常表现为心内膜炎，发生在大约5%的病例中，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）的蛋白质组成，它模仿入侵的病毒，但由于不包含必要的遗传密码，因此无法感染和引起感染。当用于免疫时，VLPs被识别为外来因子，并且颗粒表面密集排列的抗原引起强烈的免疫反应。Mologic已经开发出一种乙型肝炎病毒核心VLP的衍生物，它允许将不相关的抗原（例如来自其他病毒或细菌的抗原）附着在颗粒表面，这样它们就可以像整个病毒一样以相同的免疫原性特征显示给免疫系统。SBRI资助的“用于全球流行病的新疫苗：开发和制造”允许进一步利用这种VLP技术，以Q热（伯纳克希菌）的致病因子为目标，并与来自Dstl、PHE和Iceni诊断公司的专家进行合作，没有他们，该项目就不可能实现。该联盟现在希望进一步开发这项技术，以测试候选疫苗对抗伯纳氏杆菌攻击的效力。这将使我们能够确定扩大生产和进一步研究的最有效候选药物，以确定最佳配方和剂量。第二阶段的研究将为疫苗平台的开发提供资金，使其达到商业化、生产和GLP临床前测试的阶段。

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.