Chlamydial Immunity and Vaccine Development

衣原体免疫和疫苗开发

• 批准号: 8156879
• 负责人: HARLAN D CALDWELL
• 金额: $ 67.49万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8156879
• 关键词: Immunity; vaccine development

Chlamydia trachomatis serovars A-L3 are the causative agents of hyperendemic blinding trachoma, a largely neglected disease of the developing world, and sexually transmitted infections (STI) that are epidemic worldwide. Chlamydial STI are risk factors for HIV and a cervical cancer co-factor. Control of these important human diseases is the long term goal of this project. Towards this end our goal is to develop a safe and efficacious live attenuated vaccine to prevent these diseases. The obligate intracellular life style, complex developmental biology, and antigenic structure of chlamydiae have severally hindered progress in vaccine development. A live-attenuated vaccine (LAV) will be beneficial in circumventing these difficulties. We have made a plasmidless trachoma strain and found it to be highly attenuated for the monkey eye. Ocular infection with the LAV is immunogenic and induces solid protective immunity to challenge with virulent chlamydiae. Interestingly, LAV immunity was shown to be superior to natural infection mediated immunity. Ongoing studies are aimed at understanding differences in vaccine versus natural immunity by performing transcriptional analysis of ocular tissues. These findings should guide further vaccine studies that are capable of preferentially targeting protective versus pathology immunity.

沙眼衣原体血清vas a-l3是高流行性盲虫的病因，是发展中国家的一种很大程度上被忽视的疾病，以及全球流行病的性传播感染（STI）。衣原体性传播疾病是HIV和宫颈癌共同因素的危险因素。控制这些重要的人类疾病是该项目的长期目标。为此，我们的目标是开发一种安全有效的活衰减疫苗，以防止这些疾病。 衣原体的强制性细胞内生活方式，复杂的发育生物学和抗原结构已严重阻碍疫苗发育的进展。实时销售的疫苗（LAV）将有益于避免这些困难。我们已经制作了无质粒性沙眼菌株，发现它对猴子的眼睛高度衰减。 用LAV感染眼是免疫原性的，可诱导固体保护性免疫，以挑战有毒的衣原体。 有趣的是，LAV免疫被证明优于自然感染介导的免疫力。 正在进行的研究旨在通过对眼组织进行转录分析来了解疫苗与自然免疫的差异。 这些发现应指导能够优先靶向保护性与病理免疫的进一步疫苗研究。