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: 8357801
• 负责人: MARK K SLIFKA
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357801
• 关键词: Adult; Adverse event; Attenuated Vaccines; Cessation of life; Development; Dose; Drug Formulations; Elderly; Formaldehyde; Funding; Generations; Grant; Hydrogen Peroxide; Immune System Diseases; Immune response; Immunization; Immunocompromised Host; Individual; Infant; Infection; Life; Macaca mulatta; Mediating; Modeling; National Center for Research Resources; Paper; Plaque Assay; Primates; Principal Investigator; Publishing; Research; Research Infrastructure; 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; cost; design; immunogenicity; novel strategies; novel vaccines; vaccine efficacy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. In summary, we have successfully established a virulent YFV challenge model in rhesus macaques, designed and validated a new approach to quantify virulent YFV strains that are not amenable to traditional plaque assays, and have initiated our vaccine efficacy studies. Moreover, we have 3 papers published (or in press) and will submit 2 more papers within the next 2-6 months.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 世界卫生组织估计，城市黄热病每年造成200,000例和30,000例死亡。当前的现场YFV疫苗YF-VAX疫苗为YFV感染提供了重大保护，但疫苗的风险可能超过了收益。例如，用YF-VAX¿进行免疫接种导致每百万剂量的1至2次疫苗相关的死亡人数，包括年轻，健康的成年人死亡。不良事件发生在弱势群体（例如老年人）中，而活疫苗在其他弱势群体（例如婴儿或免疫疾病的个体）中正式禁忌。在这个项目中，我们提供了证据，表明我们已经开发了一种新型的疫苗平台，该平台为活病毒疫苗提供了有效且安全的替代方案。我们表明，与基于甲醛的灭活技术相比，使用过氧化氢增强抗原性和免疫原性的病毒灭活。使用此疫苗平台，我们建议开发一种新的YFV疫苗，用于健康个体和易受伤害的人群，这些疫苗与实时病毒疫苗有关免疫抑制的禁忌症。这项工作将涉及1）适当严格的YFV感染模型的开发，2）分析和优化灭活的YFV疫苗公式，3）3）疫苗介导的免疫复杂的表征，并保护与临床相关的致命YFV菌株的致命挑战。建立这一第二​​代YFV疫苗将代表50年来首次YFV疫苗，并为免疫学上脆弱的人群提供急需的疫苗替代品。总而言之，我们在恒河猕猴中成功建立了一个有毒的YFV挑战模型，该模型设计和验证了一种新的方法来量化不适合传统斑块阿萨斯的有毒YFV菌株，并启动了我们的疫苗效率研究。此外，我们将发表3篇论文（或在媒体上），并将在接下来的2-6个月内提交2篇论文。