Chlamydial Immunity and Vaccine Development

衣原体免疫和疫苗开发

• 批准号: 8745335
• 负责人: HARLAN D CALDWELL
• 金额: $ 88.71万
• 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/8745335
• 关键词: Attenuated; Attenuated Live Virus Vaccine; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Complex; Developmental Biology; Disease; Epidemic; Eye; Eye Infections; Future; Genitourinary system; Goals; HIV; Human; Immune; Immunity; Infection; Infertility; Life; Life Style; Malignant neoplasm of cervix uteri; Mediating; Monkeys; Plasmids; Recombinants; Risk Factors; Rodent Model; Sexually Transmitted Diseases; Solid; Structure; Subunit Vaccines; T-Lymphocyte; Trachoma; Vaccines; Virulent; Woman; Work; attenuation; human disease; immunogenic; immunogenicity; neglect; nonhuman primate; pre-clinical research; prevent; protective efficacy; transmission process; 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 plasmid deficient 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 trachoma organsims, Interestingly, LAV immunity was shown to be superior to natural infection mediated immunity. Ongoing studies are aimed at defining T cell immune correlates of solid protective immunity. These findings will guide further vaccine studies that are capable of preferentially targeting T cell protective immunity to both LAV and subunit vaccines.

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。我们已经制造了质粒缺乏沙眼菌株，并发现它对猴子的眼睛高度衰减。 通过LAV的眼部感染具有免疫原性，可诱导固体保护性免疫，以挑战有毒的沙丘瘤器官，有趣的是，LAV免疫被证明优于自然感染介导的免疫。 正在进行的研究旨在定义固体保护性免疫的T细胞免疫相关性。 这些发现将指导能够优先针对T细胞保护性免疫和亚基疫苗的疫苗研究。