Development of a synthetic multipathogen vaccine

慢性牙周炎是一种牙齿支撑组织的细菌相关炎症性疾病，它会导致牙齿支撑的破坏，最终导致牙齿脱落。这种疾病是一个重大的公共卫生问题，具有巨大的经济负担。牙龈卟啉单胞菌已被确定为慢性牙周炎发展的主要病原体。我们已经确定并表征了牙龈卟啉单胞菌的主要毒力因子；与宿主组织的结合和破坏有关的蛋白质复合物。在动物牙周炎模型中，我们已经证明这种蛋白复合物作为疫苗可以预防牙龈假单胞菌引起的疾病。我们已经确定了蛋白质复合物的区域（肽），这些区域（肽）允许细菌与宿主组织和血液蛋白结合，这些和其他复合物相关的肽在动物模型中用作疫苗时减少了疾病。最近，一个涉及齿牙霉、连翘霉和牙龈霉的联盟已经与人类牙周炎的发展密切相关。我们已经证明，在动物牙周炎模型中，这些细菌的混合物比任何一种细菌在相同的总剂量下具有更大的致病性。本项目的目的是鉴定齿状假单胞菌和连翘假单胞菌的表位，并利用我们已获得专利的技术将它们与牙龈假单胞菌的表位组合成多病原体疫苗。将研究多病原体疫苗对这三种细菌产生有效免疫反应的功效。这项工作的意义在于，我们将生产一种可能用于预防牙周炎的完全合成疫苗，而开发的平台技术可能用于与多种细菌病原体相关的一系列疾病。

Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden. The bacterium Porphyromonas gingivalis has been identified as a major pathogen in the development of chronic periodontitis. We have identified and characterised a major virulence factor of P. gingivalis; a complex of proteins which is involved in binding and destruction of host tissue. We have shown that this protein complex when used as a vaccine protects against P. gingivalis induced disease in animal periodontitis models. We have identified the regions (peptides) of the protein complex that allow the bacteria to bind to host tissue and blood proteins and these and other complex-related peptides when used as vaccines reduced disease in animal models. Recently, a consortium involving T.denticola, T.forsythia and P.gingivalis has been closely associated with the development of periodontitis in humans. We have shown that a mixture of these bacteria have greater pathogenicity in an animal periodontitis model than any one bacterium individually at the same total dose. The aim of this project is to identify epitopes in T. denticola and T. forsythia and to combine them with those of P. gingivalis into a multipathogen vaccine using techniques we have patented. The efficacy of the multipathogen vaccine to produce an immume response which is effective against the three bacteria will be investigated. The significance of this work is that we will produce a fully synthetic vaccine that may have utility in the prevention of periodontitis and the platform technology developed may have utility for a range of diseases associated with multiple bacterial pathogens.