Development of a synthetic multipathogen vaccine

合成多病原体疫苗的开发

• 批准号: nhmrc : 454475
• 负责人: A/Pr Neil O'Brien-Simpson
• 金额: $ 23.47万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/development-synthetic-multipathogen-vaccine/81198
• 关键词: Development; synthetic; multipathogen; vaccine

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.

慢性牙周炎是牙齿支持组织的细菌相关炎症性疾病，导致牙齿支持破坏，最终导致牙齿脱落。该病是重大公共卫生问题，造成巨大经济负担。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。我们已经鉴定并表征了牙龈卟啉单胞菌的主要毒力因子；参与宿主组织的结合和破坏的蛋白质复合物。我们已经证明，这种蛋白质复合物用作疫苗时，可以在动物牙周炎模型中预防牙龈卟啉单胞菌引起的疾病。我们已经确定了蛋白质复合物的区域（肽），这些区域允许细菌与宿主组织和血液蛋白质结合，并且这些肽和其他复合物相关肽在用作疫苗时可以减少动物模型中的疾病。最近，由齿垢毛霉、连翘毛霉和牙龈卟啉单胞菌组成的菌群与人类牙周炎的发生密切相关。我们已经证明，在相同总剂量下，这些细菌的混合物在动物牙周炎模型中比任何一种单独的细菌具有更大的致病性。该项目的目的是鉴定齿垢毛菌和连翘毛菌的表位，并使用我们已获得专利的技术将它们与牙龈卟啉单胞菌的表位结合成多病原体疫苗。将研究多病原体疫苗产生有效对抗三种细菌的免疫反应的功效。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全合成疫苗，并且开发的平台技术可能适用于与多种细菌病原体相关的一系列疾病。