Mucosal modified vaccinina Ankara-based plaque vaccines

粘膜改良疫苗安卡拉斑块疫苗

• 批准号: 7052479
• 负责人: Dan Thomas Stinchcomb
• 金额: $ 35.76万
• 依托单位: INVIRAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052479
• 关键词: Poxviridae; aerosols; antigens; human; immune response

DESCRIPTION (provided by applicant): Plague has devastated human and animal populations throughout history. In recent years, it has caused severe epidemics in many parts of the world, resulting in human deaths and severe economic losses. In addition, Yersinia pestis, the cause of plague, could be a devastating bioweapon. An intentional release of 50 kg of Y. pestis over a city of 5 million people could result in as many as 150,000 clinical cases and 36,000 deaths. Currently, no human vaccines are available for plague. A novel vaccine is needed that can protect against aerosolized exposure to Y. pestis. Viral vectors are among the many approaches currently being pursued to develop novel plague vaccines. Modified vaccinia Ankara (MVA) virus offers distinct advantages as a viral vaccine vector for the next generation of biodefense vaccines. Its safety and induction of mucosal immune responses has been well-documented for a variety of pathogens and MVA is being used as a second generation smallpox vaccine. In a related poxvirus vaccine vector, we demonstrated that several molecular elements significantly enhance the expression levels of Y. pestis F1 capsular antigen and augment the immune response. Our long-term goal is to optimize antigen expression by recombinant MVA and develop a highly safe mucosal MVA-based plague vaccine that protects against aerosol exposure to both Y. pestis and smallpox virus. The specific aims are as follows. 1) Construct and evaluate optimized MVA recombinant viruses that will express several Y. pestis antigens. 2) Test the efficacy of the recombinant MVA viruses for protection from aerosolized Y. pestis. 3) Evaluate vaccine protection against Y. pestfs antigen variants. 4) Evaluate the safety of the recombinant MVA/Y. pestis vaccines in immunodeficient mice. The combination of recombinant MVA vaccines that safely provides the most complete protection of mice from aerosol exposure to Y. pestis will be chosen for further analysis. In phase II, a multivalent MVA vaccine expressing the required antigens will be constructed and tested in mice and in non-human primates for protection against aerosolized Y. pestis and protection in experimental models of smallpox virus exposure.

描述（由申请人提供）：瘟疫在整个历史上摧毁了人类和动物种群。近年来，它在世界许多地方引起了严重的流行病，导致人类死亡和严重的经济损失。此外，鼠疫的原因耶尔西尼亚·佩斯蒂斯（Yersinia Pestis）可能是毁灭性的生物武器。有意释放50公斤的柴油在一个500万人的城市中可能导致多达15万个临床病例和36,000例死亡。目前，没有人类疫苗可用于鼠疫。需要一种新型的疫苗，可以防止雾化暴露于Y. Pestis。病毒载体是目前正在采用的众多方法来开发新型瘟疫疫苗的方法。修改后的Ankara（MVA）病毒提供了明显的优势，作为下一代生物污染疫苗的病毒疫苗载体。它的安全性和粘膜免疫反应的诱导已被充分记录在各种病原体中，MVA被用作第二代天花疫苗。在相关的痘病毒疫苗载体中，我们证明了几个分子元素显着提高了鼠疫杆菌F1囊膜抗原的表达水平并增强免疫反应。我们的长期目标是通过重组MVA优化抗原表达，并开发出高度安全的基于粘膜MVA的瘟疫疫苗，以防止气雾剂暴露于Pestis和天花病毒。具体目标如下。 1）构建和评估优化的MVA重组病毒，这些病毒将表达几种鼠疫抗原。 2）测试重组MVA病毒免受雾化Y. Pestis的保护的功效。 3）评估针对Y. PESTFS抗原变异的疫苗保护。 4）评估重组MVA/y的安全性。免疫缺陷小鼠中的瘟疫疫苗。将选择最完整的小鼠免受气溶胶暴露于Y的重组MVA疫苗的组合。将选择鼠疫以进行进一步分析。在II期中，将在小鼠和非人类灵长类动物中构建和测试表达所需抗原的多价MVA疫苗，以保护天花病毒暴露的实验模型中的雾化Y. pestis和保护。