Development of a P.gingivalis vaccine

牙龈卟啉单胞菌疫苗的开发

• 批准号: 6909096
• 负责人: ERIC C REYNOLDS
• 金额: $ 27万
• 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/6909096
• 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）：牙周疾病是 支撑组织的细菌相关炎症性疾病 牙齿和更具侵略性的形式，牙周炎，特征是 破坏牙齿支撑结构。当前治疗 牙周疾病是非特异性的，是基于继续去除的 通过机械手段的尺寸斑块，通常涉及手术程序。 这种正在进行的疗法是昂贵的，并且由于患者而具有可变的预后 不合规。最近的证据表明细菌 牙龈卟啉单胞菌是某些形式的主要病因学药 疾病。该应用的广泛目的是确定 牙龈疟原虫主要外膜蛋白的适用性， 通过确定的候选人进行了较早的研究，以开发定义的 重组或合成疫苗。从长远来看，这可能导致 开发有效，特定和新颖的预防性和治疗性 与牙龈疟原虫相关的牙周炎的策略。三十多个外部 已经开发了牙龈疟原虫的膜蛋白，其中六个将 为疫苗开发提供出色的候选人。具体而言，准备工作 将用于制备这些选定的牙龈疟原虫外膜蛋白 和蛋白质片段使用细菌表达系统，并确定 对这些纯化的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 如鼠类疾病模型中针对牙龈疟原虫的定义疫苗。