Vaccine Studies of the hemoglobin receptor of H. ducreyi

描述(由申请人提供)：杜热氏嗜血杆菌是生殖器溃疡下巴疾病的病原体，在世界几个地区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素。使用一种有效的疫苗，适当地管理，控制下巴，很可能会减少艾滋病毒的传播。研发这样一种疫苗是我的实验室的目标。我们建议对杜氏嗜血杆菌血红蛋白受体(HgbA)的免疫生物学和结构进行研究。HgbA的几个特性使其成为一种有吸引力的候选疫苗。HgbA是确定人类实验感染所必需的。HgbA在免疫和功能上是保守的，所有的杜氏杆菌都表达HgbA。与其他细菌的血红蛋白受体不同，HgbA不经历阶段或抗原变异。在冷藏兔软下巴感染模型上的研究，建议纯化的天然或重组的HgbA 表达的HgbA是部分有效的疫苗。进一步的疫苗研究利用猪感染H.ducreyi的模型，更接近于自然的人类感染。实验疫苗将包括从杜氏嗜血杆菌类型菌株35000中提纯的天然HgbA，或者可能是来自HgbA的合成肽。我们将测试天然HgbA抵御同源和异源挑战感染的能力。将对HgbA进行详细研究，包括了解其结构和表面暴露的HgbA的区域/残基。我们将确定地理上不同的分离株HgbA蛋白的变异性。这些研究对于更好地了解软骨软骨病的发病机制很重要，并将在几个方面促进疫苗的开发。

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.