Thermostable Inactivated Potent Yellow Fever Vaccine

摘要 黄热病是由黄热病引起的一种急性病毒性出血热 据估计，每年有20万人感染YFV病毒。约50%的 发展成严重病例的感染者将死亡。感染是 在非洲和南美洲很常见，这些地区的旅行者和居民在 感染病毒的风险很高。最近YF在非洲和南美洲的复兴 暴露出YFV疫苗供应短缺，不足以对抗这一主要公众 健康问题。 在这个项目中，通用稳定技术(UST)与加州大学合作 德克萨斯医疗分部(UTMB)将应用科大的新方法开发 从野生型YFV开始的耐热、灭活和有效的YF疫苗。这个 YFV将稳定在环境温度(AT)下，使用科大专利的“保存方式” 汽化“(PBV)技术，随后在AT使用电子束灭活 (Eb)生产黄热病灭活疫苗的辐照程序。 已经发现EB失活是通过病毒核酸损伤来灭活的，而不是 影响病毒表面结构，从而保持表位或抗原性的完整性 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：生产耐热、电子束(EB)灭活黄热病 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的短期测试。 ·目的3.评估YFV候选疫苗的保护效果 仓鼠模型中的嗜内性YF。 我们的直接目标是证明一种安全、有效、低成本的热稳定性的可行性。 黄热病病毒疫苗。在这个项目中开发的技术可以 最终为快速开发安全、耐热、 以及针对其他新出现的疾病的有效疫苗。

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.