Salmonella anti-influenza DNA & antigen delivery vaccine

沙门氏菌抗流感DNA

• 批准号: 6957620
• 负责人: ROY CURTISS III
• 金额: $ 27.46万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-16 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957620
• 关键词: Salmonella vaccines; attenuated microorganism; cross immunity; emerging infectious disease; gene delivery system; guinea pigs; influenza vaccines; laboratory mouse; laboratory rabbit; mucosal immunity; oral administration; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): Influenza viruses display antigenic drift necessitating development of updated vaccines each year. Misjudgment or absence of appropriate information can lead to design and production of vaccines with marginal ability to protect against the prevailing strains. Influenza also undergo genome reassansortment by co-infection of animal host cells with two different influenza viruses. Since there are influenza strains that infect birds, swine, horses and humans and since these host-adapted viruses have different antigenic components, genome reassortment can generate influenza strains that have never existed before. Consequently, such new reassortment viruses could cause an influenza pandemic, with potential to cause some 300 million world-wide deaths. The economic consequences of such a pandemic due to morbidity, health care delivery and in burying the deceased would be staggering. Since methods exist to generate such reassortment viruses in the laboratory or by willful co-infection of cells or animals, it must be appreciated that influenza could become a significant bioweapon. Another problem with current technology in making influenza vaccines is the reliance on using embryonated eggs that is time-consuming (taking four months), has low productivity and, most troublesome, cannot be used when needing to make vaccines with some avian influenza components. Our objective is to design, construct and evaluate a novel inexpensive rapidly modifiable vaccine for oral needle-free vaccination to deliver DNA vaccines and protective antigens/epitopes to induce protective immunity, including mucosal immunity, in children and adults to prevent infection by influenza viruses with avian and human antigenic components. In addition to relying on inducing protective immunity to HA antigens, we will thoroughly investigate the potential to induce a longer lasting cross-protective cellular immunity by delivery of conserved antigens containing T-cell epitopes. The vaccine delivery system employs attenuated Salmonella strains with special newly developed features to maximize colonization of lymphoid tissues and that display a regulated delayed lysis in vivo phenotype to release DNA vaccines encoding influenza hemagglutinin antigens in the cytosol of host cells and deliver protective antigens/epitopes to other tissues.

描述(申请人提供)：流感病毒表现出抗原漂移，需要每年开发更新的疫苗。误判或缺乏适当信息可能导致疫苗的设计和生产，这些疫苗对流行毒株的保护能力微乎其微。流感还会通过动物宿主细胞与两种不同的流感病毒混合感染而进行基因组重组。由于有感染鸟类、猪、马和人类的流感病毒株，而且这些宿主适应的病毒具有不同的抗原成分，基因组重组可能会产生以前从未存在过的流感病毒株。因此，这种新的重新组合病毒可能会导致流感大流行，有可能导致全球约3亿人死亡。由于发病率、医疗服务的提供和死者的埋葬，这种大流行的经济后果将是惊人的。由于存在在实验室或通过故意合并感染细胞或动物来产生这种重新组合病毒的方法，必须认识到，流感可能成为一种重要的生物武器。目前制造流感疫苗的技术的另一个问题是依赖于使用胚胎卵子，这很耗时(需要四个月)，生产率低，最麻烦的是，当需要制造含有某些禽流感成分的疫苗时，无法使用。我们的目标是设计、构建和评价一种新型廉价、可快速修改的口服无针疫苗，以提供DNA疫苗和保护性抗原/表位，以诱导儿童和成人的保护性免疫，包括粘膜免疫，以防止含有禽流感和人类抗原成分的流感病毒感染。除了依赖于诱导对HA抗原的保护性免疫外，我们还将深入研究通过传递包含T细胞表位的保守抗原来诱导更持久的交叉保护性细胞免疫的可能性。疫苗递送系统使用具有特殊新开发特征的减毒沙门氏菌菌株，以最大限度地在淋巴组织中定植，并在体内表现出受调控的延迟裂解表型，在宿主细胞的胞浆中释放编码流感血凝素抗原的DNA疫苗，并将保护性抗原/表位输送到其他组织。