Chlamydial Immunity and Vaccine Development

沙眼衣原体血清型A-L3是高流行性致盲性沙眼（一种在发展中国家被严重忽视的疾病）和性传播感染（STI）的病原体，在世界范围内流行。衣原体性传播感染是艾滋病毒的危险因素，也是宫颈癌的辅助因素。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减毒活疫苗来预防这些疾病。 衣原体特有的细胞内生活方式、复杂的发育生物学和抗原结构阻碍了疫苗的发展。减毒活疫苗（LAV）将有助于规避这些困难。我们已经制备了一种无质粒沙眼菌株，并发现它对猴眼的毒性高度减弱。 LAV的眼部感染具有免疫原性，并诱导对强毒衣原体攻击的固体保护性免疫。 有趣的是，LAV免疫显示出上级于天然感染介导的免疫。 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天然免疫的差异。 这些发现应该指导进一步的疫苗研究，能够优先针对保护性免疫而不是病理性免疫。

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.