Development of a P.gingivalis vaccine

牙龈卟啉单胞菌疫苗的开发

• 批准号: 7056200
• 负责人: ERIC C REYNOLDS
• 金额: $ 26.37万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056200
• 关键词: Bacteroides gingivalis; active immunization; antigen antibody reaction; bacterial proteins; biological models; biotechnology; cell proliferation; chimeric proteins; clinical research; drug screening /evaluation; enzyme linked immunosorbent assay; laboratory mouse; mass spectrometry; membrane proteins; molecular cloning; nuclear magnetic resonance spectroscopy; nucleic acid probes; periodontium disorder; protein purification; recombinant proteins; site directed mutagenesis; synthetic peptide; synthetic vaccines; tissue /cell culture; transfection /expression vector; vaccine development

DESCRIPTION (provided by applicant): Periodontal diseases are bacterial-associated inflammatory diseases of the supporting tissues of the teeth and the more aggressive forms, periodontitis, are characterized by the destruction of the tooth supporting structures. Current treatments for the periodontal diseases are nonspecific and are based on the continued removal of subgingival plaque by mechanical means, often involving surgical procedures. This ongoing therapy is costly and has a variable prognosis due to patient non-compliance. Recent evidence has demonstrated that the bacterium Porphyromonas gingivalis is a major etiologic agent of some forms of these diseases. The broad objective of this application is to determine the suitability of the major outer membrane proteins of P. gingivalis, that the earlier studies by identified candidates for the development of a defined recombinant or synthetic vaccine. In the long-term, this may lead to the development of effective, specific and novel prophylactic and therapeutic strategies for P. gingivalis-associated periodontitis. Over thirty outer membrane proteins of P. gingivalis have been developed and six of these will make excellent candidates for vaccine development. Specifically, a preparation will be used to prepare these selected P. gingivalis outer membrane proteins and protein fragments using a bacterial expression system and determine the immune response to these purified recombinant proteins in mice. A further Aim is the preparation of synthetic peptide multivalent constructs based on immunogenic sequences of the outer membrane proteins. The recombinant proteins, protein fragments and synthetic peptide multivalent constructs will be tested as defined vaccines against P. gingivalis in murine models of disease.

描述（由申请人提供）： 牙周病是 支持组织的细菌相关炎症性疾病 牙齿和更具侵袭性的牙周炎的特点是 牙齿支撑结构的破坏。目前的治疗方法为 牙周病是非特异性的，并且基于牙周病的持续去除 通过机械方法清除龈下菌斑，通常涉及外科手术。 这种正在进行的治疗费用昂贵，并且由于患者的不同而具有不同的预后 不遵守规定。最近的证据表明，该细菌 牙龈卟啉单胞菌是某些形式的这些疾病的主要病原体 疾病。该应用程序的主要目标是确定 牙龈卟啉单胞菌主要外膜蛋白的适用性， 早期研究由确定的候选者进行，以开发明确的 重组或合成疫苗。从长远来看，这可能会导致 开发有效、特异和新颖的预防和治疗药物 牙龈卟啉单胞菌相关牙周炎的治疗策略。三十多个外 牙龈卟啉单胞菌的膜蛋白已经开发出来，其中六种将 成为疫苗开发的优秀候选者。具体来说，准备 将用于制备这些选定的牙龈卟啉单胞菌外膜蛋白 和蛋白质片段使用细菌表达系统并确定 小鼠体内对这些纯化重组蛋白的免疫反应。进一步的目标 是基于合成肽多价构建体的制备 外膜蛋白的免疫原性序列。重组蛋白， 将测试蛋白质片段和合成肽多价构建体 定义为针对小鼠疾病模型中的牙龈卟啉单胞菌疫苗。

项目成果

The role of the RgpA-Kgp proteinase-adhesin complexes in the adherence of Porphyromonas gingivalis to fibroblasts.

RgpA-Kgp 蛋白酶-粘附素复合物在牙龈卟啉单胞菌粘附至成纤维细胞中的作用。

• DOI: 10.1099/mic.0.2008/019943-0
• 发表时间: 2008
• 期刊: Microbiology (Reading, England)
• 作者: Pathirana,RishiD;O'Brien-Simpson,NeilM;Visvanathan,Kumar;Hamilton,JohnA;Reynolds,EricC
• 通讯作者: Reynolds,EricC