Thermostable Inactivated Potent Yellow Fever Vaccine

耐热灭活强效黄热病疫苗

• 批准号: 10437039
• 负责人: Victor Bronshtein
• 金额: $ 29.69万
• 依托单位: UNIVERSAL STABILIZATION TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-23 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437039
• 关键词: Acute; Adverse reactions; Affect; Africa; Age-Years; Area; Attenuated; Blood Chemical Analysis; Body Weight; Carbohydrates; Clinic; Clinical Chemistry; Cold Chains; Collaborations; Communicable Diseases; Contracts; Development; Disease; Elderly; Electron Beam; Epidemic; Epitopes; Formulation; Freeze Drying; Functional disorder; Glass; Goals; Hamsters; Hour; Immobilization; Immune system; Immunocompromised Host; Individual; Infection; Investigation; Laboratories; Legal patent; Measures; Medical; Modeling; Nucleic Acids; Organ; Patients; Persons; Phase; Pregnant Women; Procedures; Process; Production; Public Health; Research; Rubber; Serum; Small Business Technology Transfer Research; South America; Structure; Surface; Technology; Temperature; Testing; Texas; Tissues; Travel; Universities; Vaccinated; Vaccination; Vaccines; Vacuum; Vial device; Viral Hemorrhagic Fevers; Viral Load result; Viral Proteins; Virus; Virus Replication; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus; aged; cost; fighting; high risk; innovative technologies; irradiation; mortality; neutralizing antibody; new technology; novel strategies; pathogen; pregnant; preservation; prevent; process optimization; protective effect; protective efficacy; respiratory; seal; stability testing; success; thermostability; vaccine candidate; vaccine evaluation; vaporization

Summary Yellow Fever (YF) is an acute viral hemorrhagic fever disease caused by Yellow Fever virus (YFV) and an estimated 200,000 YF infections occur annually. Approximately 50% of infected individuals that develop a severe case of the disease will die. The infection is common in Africa and South America, and travelers and residents of those areas are at high risk of contracting the virus. A recent resurgence of YF in Africa and South America has exposed the YFV vaccine supply shortage that is insufficient to fight this major public health problem. In this project, Universal Stabilization Technologies (UST) in collaboration with University of Texas Medical Branch (UTMB) will apply UST’s novel approach for development of thermostable, inactivated, and potent vaccine against YF starting with wild-type YFV. The YFV will be stabilized at ambient temperatures (AT) using UST’s patented “Preservation by Vaporization” (PBV) technology and subsequently inactivated at AT using electron beam (EB) irradiation procedure to produce inactivated and potent vaccine against Yellow Fever. The EB inactivation has been found to inactivate through virus nucleic acid damage without affecting virus surface structures, thus preserving integrity of epitopes, or antigenic determinants recognized by the immune system, while preventing virus replication. The specific aims for this project are the following: • Aim 1: Produce thermostable, electron beam (EB) inactivated Yellow Fever vaccine candidate. • Aim.2. Perform long-term stability testing at low, medium, and high ambient temperatures: 4⁰C. 25⁰C. 37⁰C and short-term testing at 70⁰C. • Aim 3. Evaluate protective efficacy of the YFV vaccine candidate against viscerotropic YF in a hamster model. Our immediate goal is to prove feasibility of a safe, effective, low-cost thermostable vaccine against Yellow Fever virus. The technologies developed in this project could eventually provide a platform technology for quick development of safe, thermostable, and effective vaccines against other emerging diseases.

概括 黄热病（Yellow Fever，YF）是由黄热病引起的一种急性病毒性出血热病 病毒（YFV），估计每年发生 200,000 例 YF 感染。大约 50% 病情严重的感染者将会死亡。感染是 在非洲和南美洲很常见，这些地区的旅行者和居民 感染病毒的风险很高。最近，YF 在非洲和南美洲卷土重来 暴露YFV疫苗供应短缺不足以对抗这一重大公众 健康问题。 在这个项目中，通用稳定技术（UST）与大学合作 德克萨斯医学分会 (UTMB) 将应用 UST 的创新方法来开发 以野生型 YFV 为起始原料的耐热、灭活且有效的 YF 疫苗。这 YFV 将使用 UST 的专利“Preservation by 汽化”(PBV) 技术，随后使用电子束在 AT 处灭活 (EB) 辐照程序生产灭活的、有效的黄热病疫苗。 已发现EB失活是通过病毒核酸损伤而失活，无需 影响病毒表面结构，从而保持表位或抗原的完整性 免疫系统识别的决定因素，同时防止病毒复制。 该项目的具体目标如下： • 目标 1：产生耐热、电子束 (EB) 灭活的黄热病 候选疫苗。 • 目标2。在低、中、高环境下执行长期稳定性测试 温度：4⁰C。 25⁰C。 37⁰C 和 70⁰C 短期测试。 • 目标 3. 评估 YFV 候选疫苗的保护功效 仓鼠模型中的内脏 YF。 我们的近期目标是证明安全、有效、低成本的热稳定的可行性 黄热病病毒疫苗。该项目开发的技术可以 最终为快速开发安全、耐高温、 以及针对其他新出现疾病的有效疫苗。