Development of a synthetic multipathogen vaccine

慢性牙周炎是一种与细菌相关的牙齿支持组织炎症性疾病，它会导致牙齿支架的破坏，最终导致牙齿脱落。这种疾病是一个重大的公共卫生问题，带来了巨大的经济负担。牙龈卟啉单胞菌已被鉴定为慢性牙周炎的主要病原菌。我们已经确定并表征了牙龈假单胞菌的一个主要毒力因子；一种与宿主组织结合和破坏有关的蛋白质复合体。我们已经证明，这种蛋白质复合体作为疫苗使用时，可以在动物牙周炎模型中预防牙周炎假单胞菌引起的疾病。我们已经确定了允许细菌与宿主组织和血液蛋白结合的蛋白质复合体的区域(肽)，以及这些和其他复合体相关的多肽，当用作疫苗时，可以在动物模型中减少疾病。最近，一个由登革热、连翘和牙龈假单胞菌组成的联合体与人类牙周炎的发生密切相关。我们已经证明，在动物牙周炎模型中，这些细菌的混合物在相同的总剂量下比单独的任何一种细菌具有更强的致病性。该项目的目的是识别齿弓形虫和连翘中的表位，并利用我们的专利技术将它们与牙龈假单胞菌的表位结合成一种多病原疫苗。多病原体疫苗产生对这三种细菌有效的免疫反应的有效性将被调查。这项工作的意义在于，我们将生产一种可能在预防牙周炎方面有用的全合成疫苗，所开发的平台技术可能对与多种细菌病原体相关的一系列疾病有用。

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.