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 A-L3 血清型是高地方性致盲性沙眼（一种在发展中国家很大程度上被忽视的疾病）和在世界范围内流行的性传播感染 (STI) 的病原体。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。 衣原体的专性细胞内生活方式、复杂的发育生物学和抗原结构都阻碍了疫苗开发的进展。减毒活疫苗（LAV）将有助于克服这些困难。我们制备了一种质粒缺陷型沙眼菌株，发现它对猴眼具有高度减毒作用。 LAV 的眼部感染具有免疫原性，并诱导坚固的保护性免疫来抵抗有毒的沙眼微生物。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确定固体保护性免疫的 T 细胞免疫相关性。 这些发现将指导进一步的疫苗研究，这些研究能够优先针对 LAV 和亚单位疫苗的 T 细胞保护性免疫。