Vaccine Studies of the hemoglobin receptor of H. ducreyi

描述（由申请方提供）：杜克雷嗜血杆菌是生殖器溃疡疾病软下疳的病原体，是全球多个地区的重大公共卫生问题。在非洲、亚洲和其他发展中国家，它是异性性传播艾滋病毒的一个重要辅助因素。控制软下疳，使用有效的疫苗，适当管理，可能会减少艾滋病毒的传播。我的实验室的目标就是研制这样一种疫苗。 本文拟对血吸虫血红蛋白受体（HgbA）的免疫生物学和结构进行研究。ducreyi。 HgbA的几个属性使其成为一种有吸引力的候选疫苗。HgbA是建立人类实验感染所必需的。HgbA在免疫学和功能上是保守的，所有H.与来自其他细菌的血红蛋白受体不同，HgbA不经历相位或抗原变异。 在软下疳感染的冷冻兔模型中的研究表明，纯化的天然HgbA或重组HgbA可用于治疗软下疳感染。 表达的HgbA是部分有效的疫苗。进一步的疫苗研究利用了杜克雷血吸虫感染的猪模型，该模型更接近于自然的人类感染。实验疫苗将由来自H. ducreyi型菌株35000，或可能的衍生自HgbA的合成肽。 我们将测试天然HgbA对同源和异源攻击感染的保护能力。 将对HgbA进行详细研究，包括了解其结构和表面暴露的HgbA区域/残基。我们将确定从地理上不同的分离株的HgbA蛋白的变异性。这些研究对于更好地理解软下疳的发病机制是重要的，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.