Vaccine Platforms

疫苗平台

• 批准号: 7706286
• 负责人: RONALD G CRYSTAL
• 金额: $ 97.69万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7706286
• 关键词: Adenovirus Vector; Adenoviruses; Animals; Anthrax disease; Antibodies; Antigen Presentation Pathway; Antigens; Area; Attenuated; Bacillus (bacterium); Bacillus anthracis; Bioterrorism; Burkholderia mallei; Calmette-Guerin Bacillus; Categories; Complex; Development; Disease; Ebola virus; Effectiveness; Event; Exhibits; Facility Construction Funding Category; Generic Drugs; Genetic; Glanders; Goals; Health Personnel; Human; Immune; Immune response; Immunity; Immunization; Immunologic Memory; Infectious Agent; Intervention; Life; Medical; Military Personnel; Morbidity - disease rate; Mucosal Immune Responses; Mycobacterium tuberculosis; Newcastle disease virus; Numbers; Pathogenicity; Pneumonic Plague; Polyvalent Vaccine; Population; Proteins; Purpose; Range; Recombinants; Research Personnel; Rosa; Safety; Salmonella typhimurium; Stomatitis; System; Toxin; Type III Secretion System Pathway; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral Vector; Virus; West Nile virus; Yersinia pestis; bacterial vector; base; biodefense; cost; design; emergency service responder; gene cloning; mortality; pathogen; prevent; response; vector

Vaccines remain the most cost-effective medical intervention known to prevent morbidity and mortality caused by infectious agents. Vaccines may also become a major component in the armamentarium to protect ourselves against the deliberate release of bioterrorism agents. The goal of this thematic area is to develop, characterize and optimize live viral and bacterial vectors to deliver antigens of bioterrorism agents, ultimately resulting in the protection of humans against a variety of threatening diseases. We will concentrate on the development of vectors, because traditional vaccine approaches cannot easily be applied to many of the category A, B and C agents. The first subproject (Crystal) aims at the use of recombinant adenovirus vectors expressing the Bacillus antkracis PA antigen and/or a single chain antibody against this antigen. Such a dual approach may provide instant protection via expression of the antibody, as well as long term immunity against the toxin elaborated by anthrax. The second (Rose) and third (Palese) subprojects take advantage of recombinant vesicular stomatitis virus and recombinant Newcastle disease virus, respectively. Humans have no immunity against either of these viruses and their pathogenicity in humans is low or absent, making them promising vectors to use in developing effective vaccines against such category A pathogens as B. anthracis, Yersinia pestis, and Ebola virus. It is also hoped that these viral vectors can be used as generic vehicles for inducing protective immune responses against a broad range of pathogens. We will also study bacterial vectors, including Salmonella typhimurium (subproject 4. Galan) which offers several advantages over other antigen delivery systems, including a strong mucosal immune response. Avirulent strains of S. typhimurium will be constructed which deliver, through their type III secretion system, protective antigens against B. anthracis, Y. pestis, and Burkholderia mallei. Appropriate animal systems will be used to evaluate the ability of such vectors to protect against anthrax, pneumonic plague and glanders. Subproject 5 (Jacobs) will make use of other bacterial vectors (recombinant BCG strain of M. tuberculosis and attenuated strains of M. tuberculosis) to express different antigens, including the West Nile virus E and NS-1 proteins. By trying different vector approaches against the same pathogen, we hope to set up synergistic relationships that should allow us to quickl2¿ compare and develop more effective vaccines against these potential agents ofbioterrorism.

疫苗仍然是最具成本效益的医疗干预措施，以预防发病率和死亡率 由传染剂引起。疫苗也可能成为保护的主要组成部分以保护 我们反对故意释放生物恐怖主义者。这个主题领域的目标是发展， 表征并优化活病毒和细菌向量以提供生物恐怖剂的抗原， 最终导致保护人类免受各种威胁性疾病的影响。我们将集中精力 关于向量的开发，因为传统的疫苗方法无法轻易应用于许多 A类，B和C代理。第一个子标准（晶体）旨在使用重组腺病毒 表达抗原抗原抗原的芽孢杆菌抗原杆菌的载体。 这种双重方法可以通过表达抗体以及长期来提供即时保护 对炭疽病阐述的毒素的免疫力。第二个（玫瑰）和第三个（Palese）submojects占用 重组囊泡口腔炎病毒和重组纽卡斯尔病毒的优势， 人类对这两种病毒均无免疫力，其在人类中的致病性是 低或缺席，使它们承诺向量用于开发有效疫苗针对此类类别 病原体作为炭疽芽孢杆菌，耶尔森氏菌和埃博拉病毒。也希望这些病毒载体可以是 用作诱导的受保护免疫复杂的通用车辆，以针对广泛的病原体。我们 还将研究细菌载体，包括鼠伤寒沙门氏菌（subproject 4.Galan） 比其他抗原递送系统的几个优势，包括强粘膜免疫响应。 将建造鼠伤寒链霉菌的毒气菌株，该菌株通过其III型分泌系统传递 防护抗原针对炭疽芽孢杆菌，Y. Pestis和Burkholderia Mallei。适当的动物系统将 用于评估此类媒介预防炭疽，肺鼠疫和地面的能力。 第5（Jacobs）将使用其他细菌载体（重组BCG结核分枝杆菌菌株 并减弱结核分枝杆菌的菌株）以表达不同的抗原，包括西尼罗河病毒E和 NS-1蛋白。通过尝试针对同一病原体的不同矢量方法，我们希望建立协同作用 关系应该使我们能够快速2€比较并开发更有效的疫苗 生物恐怖主义的潜在药物。