YELLOW FEVER VACCINATION OF THE AGED AND IMMUNOCOMPROMISED

老年人和免疫力低下者的黄热病疫苗接种

• 批准号: 8173291
• 负责人: MARK K SLIFKA
• 金额: $ 9.51万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173291
• 关键词: Adult; Adverse event; Attenuated Vaccines; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Development; Dose; Drug Formulations; Elderly; Formaldehyde; Funding; Generations; Grant; Hydrogen Peroxide; Immune System Diseases; Immune response; Immunization; Immunocompromised Host; Individual; Infant; Infection; Institution; Life; Mediating; Modeling; Research; Research Personnel; Resources; Risk; Source; Techniques; United States National Institutes of Health; Vaccination; Vaccines; Viral Vaccines; Virulent; Virus; Virus Inactivation; Vulnerable Populations; Work; World Health Organization; Yellow Fever; aged; base; clinically relevant; immunogenicity; novel vaccines

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The World Health Organization has estimated that urban yellow fever causes 200,000 cases and 30,000 deaths annually. The current live YFV vaccine, YF-VAX¿, has provided significant protection against YFV infection but the risks of vaccination may outweigh the benefits. For instance, immunization with YF-VAX¿ results in 1 to 2 vaccine-associated deaths per million doses administered  including fatalities in young, otherwise healthy adults. Adverse events occur at much higher rates in vulnerable populations such as the elderly, and the live vaccine is formally contraindicated in other vulnerable populations such as infants or individuals with immune disorders. In this project, we present evidence demonstrating that we have developed a novel vaccine platform that provides an effective and safe alternative to live virus vaccines. We show that virus inactivation using hydrogen peroxide enhances antigenicity and immunogenicity in comparison with other approaches such as formaldehyde-based inactivation techniques. Using this vaccine platform, we propose the development of a new YFV vaccine for use in both healthy individuals and vulnerable populations that have contraindications for immunization with live viral vaccines. This work will involve 1) development of an appropriately rigorous YFV infection model, 2) analysis and optimization of an inactivated YFV vaccine formulation, and 3) characterization of vaccine-mediated immune responses and protection against lethal challenge with clinically relevant strains of virulent YFV. The establishment of this second-generation YFV vaccine will represent the first advance in YFV vaccination in 50 years and provide a much needed vaccine alternative for immunologically vulnerable populations.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 世界卫生组织估计，城市黄热病每年导致 20 万例病例和 3 万人死亡。目前的 YFV 活疫苗 YF-VAX¿ ，提供了针对 YFV 感染的显着保护，但疫苗接种的风险可能大于益处，例如，使用 YF-VAX 进行免疫接种。每注射 100 万剂疫苗，就会导致 1 至 2 例与疫苗相关的死亡，其中包括年轻人和其他健康成年人的死亡。在老年人等弱势群体中，不良事件的发生率要高得多，而且活疫苗在其他弱势群体中被正式禁用。在这个项目中，我们提供了证据，证明我们已经开发出一种新型疫苗平台，可以提供活病毒疫苗的有效且安全的替代品。我们表明，与活病毒疫苗相比，使用过氧化氢灭活病毒可以增强抗原性和免疫原性。其他的使用这种疫苗平台，我们建议开发一种新的 YFV 疫苗，用于有活病毒疫苗免疫禁忌的个人和弱势群体。适当严格的 YFV 感染模型，2) 灭活 YFV 疫苗配方的分析和优化，以及 3) 疫苗介导的免疫反应的表征以及针对临床相关毒株致命攻击的保护YFV。第二代 YFV 疫苗的建立将代表 50 年来 YFV 疫苗接种的首次进展，并为免疫脆弱人群提供急需的疫苗替代方案。