Vaccine Studies of the hemoglobin receptor of H. ducreyi

杜克雷嗜血杆菌血红蛋白受体的疫苗研究

• 批准号: 6847811
• 负责人: CHRISTOPHER ELKINS
• 金额: $ 21.15万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6847811
• 关键词: Haemophilus; antibacterial antibody; antibody formation; bacterial proteins; bacterial vaccines; biotechnology; cell surface receptors; clinical research; disease /disorder model; genetic polymorphism; genetic strain; helper T lymphocyte; hemoglobin; human subject; immunomodulators; microorganism immunology; protein structure; sexually transmitted diseases; swine; vaccine development

DESCRIPTION (provided by applicant): Haemophilus ducreyi, the etiologic agent of the genital ulcer disease chancroid, is a significant public health problem in several regions worldwide. In Africa, Asia and other developing countries, it is an important cofactor for the heterosexual transmission of HIV. Control of chancroid, using an effective vaccine that is properly administered, would likely reduce HIV transmission. It is the goal of my laboratory to develop such a vaccine. We propose studies on the immunobiology and structure of the hemoglobin receptor (HgbA) of H. ducreyi. Several attributes of HgbA make it an attractive vaccine candidate. HgbA is required to establish human experimental infection. HgbA is conserved immunologically and functionally and all H. ducreyi express it. Unlike hemoglobin receptors from other bacteria, HgbA does not undergo phase or antigenic variation. Studies in the chilled rabbit model of chancroid infection, suggest purified native HgbA or recombinantly expressed HgbA are partially effective vaccines. Further vaccine studies utilizing the Swine model of H.ducreyi infection, that more closely resembles natural human infection. Experimental vaccines will consist of purified native HgbA from H. ducreyi type strain 35000, or possibly synthetic peptides derived from HgbA. We will test the ability of native HgbA to protect against a homologous and heterologous challenge infection. Detailed studies will be undertaken on HgbA including understanding its structure and regions/residues of HgbA that are surface-exposed. We will determine the variability of the HgbA protein from geographically diverse isolates. These studies are important for better understanding of chancroid pathogenesis and will facilitate vaccine development in several aspects.

描述（由申请人提供）：生殖器性溃疡病冠状动脉疾病的病因学代理Heamophilus Ducreyi在全球多个地区都是一个重大的公共卫生问题。在非洲，亚洲和其他发展中国家，它是艾滋病毒异性传播的重要辅助因子。使用适当管理的有效疫苗控制牙头治疗可能会减少HIV传播。我的实验室是开发这种疫苗的目标。 我们提出了有关H. ducreyi的血红蛋白受体（HGBA）的免疫生物学和结构的研究。 HGBA的几个属性使其成为有吸引力的疫苗候选者。需要HGBA建立人类实验感染。 HGBA在免疫学和功能上是保守的，所有H. ducreyi表示。 与其他细菌的血红蛋白受体不同，HGBA不会发生相或抗原差异。 在chancroid感染的冷藏兔模型中的研究表明，纯化的天然HGBA或重组 表达的HGBA是部分有效的疫苗。进一步的疫苗研究利用猪的猪模型，与天然人类感染更相似。实验性疫苗将由来自H. diucreyi型菌株35000的纯化天然HGBA，或者可能是源自HGBA的合成肽。 我们将测试天然HGBA防止同源和异源挑战感染的能力。 将对HGBA进行详细的研究，包括了解其结构和HGBA的区域/残基。我们将确定HGBA蛋白从地理上不同的分离株中的变异性。这些研究对于更好地理解牙冠发病机理非常重要，并将促进多个方面的疫苗发育。