Chancroid Human Challenge Unit (CHCU)

杜雷伊嗜血杆菌引起下巴，这是一种生殖器溃疡疾病，有助于艾滋病毒-1的传播。虽然 下巴症在美国很少见，在非洲、亚洲和拉丁美洲持续存在。H.Dureyi已经获得了 许多抗生素耐药因素，唯一有效的治疗方案是大环内酯类，喹诺酮类或 头孢曲松。如果杜氏杆菌获得编码超广谱β-内酰胺酶和喹诺酮类药物的质粒 耐药，大环内酯类药物将是唯一可用的治疗方法。因此，了解杜氏杆菌的致病机理 这对于制定控制软骨病的替代战略仍然很重要。大部分都是 杜氏艾美耳球虫的致病机制源于对人类志愿者进行接种的实验 手臂上有35000马力的应变。人体模型模拟了疾病的脓疱期的下巴。 杜氏杆菌在自然感染和实验感染中与宿主细胞的关系相似， 证实了该模型与自然疾病高度相关。该模型区分了致命的、 部分减毒和完全减毒的35000HP突变体，并帮助鉴定了血红蛋白 受体，HgbA，作为一个基本的疫苗候选。生物统计核心所做的分析导致了 令人兴奋的发现，人类对杜氏杆菌感染具有不同的易感性；不同的易感性 与不同的树突状细胞对生物体的反应有关。项目2寻求继续一个独特的 在下巴人类挑战赛单元进行的一系列人体接种实验。临床试验，如 项目2中提出的只能由U01或U19机制支持，项目2满足 通过为领导STI CRC的多名调查人员提供服务，实现STI CRC网络的广泛协作目标 项目、ROI、R21、KOBS或需要初步数据才能获得资金。项目2的具体目标是 1)测试同基因突变/亲本对，以评估关于候选人贡献的假设 疾病进展的毒力决定因素，2)用亲本毒株感染志愿者以检验假设 关于杜氏杆菌的致病机制、宿主反应和人类对感染的不同易感性 进行L阶段/11阶段候选疫苗的概念验证、安全性和免疫相关性研究。

Haemophilus ducreyi causes chancroid, a genital ulcer disease that facilitates HIV-1 transmission. Although rare in the United States, chancroid persists in Africa, Asia and Latin America. H. ducreyi has acquired many antibiotic resistance factors, and the only effective treatment regimens are macrolides, quinolones or ceftriaxone. If H. ducreyi acquires plasmids that encode extended spectrum p-lactamases and quinolone resistance, macrolides will be the only available therapy. Thus, understanding the pathogenesis of H. ducreyi remains important for the development of alternative strategies for control of chancroid. Most of what is known about H. ducreyi pathogenesis is derived from experiments in which human volunteers are inoculated on the arm with strain 35000HP. The human model mimics chancroid through the pustular stage of disease. The relationships between H. ducreyi and host cells are similar in natural and experimental infection, confirming that the model is highly relevant to natural disease. The model discriminates among virulent, partially attenuated and fully attenuated mutants of 35000HP and has helped identify the hemoglobin receptor, HgbA, as a rationale vaccine candidate. Analyses done by the Biostatistical Core led to the exciting discovery that humans are differentially susceptible to H. ducreyi infection; differentially susceptibility is associated with distinct dendritic cell responses to the organism. Project 2 seeks to continue a unique series of human inoculation experiments in the Chancroid Human Challenge Unit. Clinical trials such as those proposed in Project 2 can only be supported by U01 or U19 mechanisms, and Project 2 fulfills the broad collaborative goal of the STI CRC network by serving multiple investigators who lead STI CRC projects, ROIs, R21s, KOBs or need preliminary data to secure funding. The specific aims of Project 2 are to 1) test isogenic mutant/parent pairs to evaluate hypotheses concerning the contribution of candidate virulence determinants to disease progression, 2) infect volunteers with the parent strain to test hypotheses about H. ducreyi pathogenesis, host responses and differential human susceptibility to infection and 3) perform phase l/ll proof of concept safety and correlates of immunity studies of candidate vaccines.