Salmonella anti-influenza DNA & antigen delivery vaccine

沙门氏菌抗流感DNA

• 批准号: 7174221
• 负责人: ROY CURTISS III
• 金额: $ 71.2万
• 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/7174221
• 关键词: Adult; Animals; Antigens; Attenuated; Avian Influenza; Biological Containment; Birds; Cells; Cellular Immunity; Cessation of life; Child; Collection; Cytolysis; Cytosol; DNA; DNA Vaccines; DNA delivery; Development; Economics; Epitopes; Equus caballus; Exhibits; Family suidae; Genome; Genome Components; Genotype; Human; Human Volunteers; Immune response; Immunity; Infection; Infection prevention; Influenza; Influenza Hemagglutinin; Laboratories; Lead; Lymphoid Tissue; Methods; Morbidity - disease rate; Mucosal Immunity; Mus; Mutation; National Institute of Allergy and Infectious Disease; Needles; Nucleosome Core Particle; Particulate; Phenotype; Plasmid Cloning Vector; Productivity; Recombinants; Reliance; Safety; Salmonella; Salmonella typhi; Salmonella typhimurium; Seasons; System; T-Lymphocyte Epitopes; Technology; Testing; Time; Tissues; To specify; Toxicity Tests; Type III Secretion System Pathway; United States Food and Drug Administration; Update; Vaccination; Vaccine Production; Vaccines; Virus; Week; anti-influenza; biothreat; design; design and construction; desire; egg; flu; health care delivery; in vivo; influenza virus vaccine; influenzavirus; novel; oral vaccine; pandemic disease; pandemic influenza; response; vaccine delivery; vaccine development; vector

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（由申请人提供）：流感病毒显示抗原漂移，每年需要开发更新的疫苗。错误的判断或缺乏适当的信息会导致疫苗的设计和生产具有边缘能力，以防止现行菌株。流感还通过与两种不同的流感病毒共同感染动物宿主细胞，可以进行基因组的态度。由于有流感菌株感染鸟类，猪，马和人类，并且这些适应宿主的病毒具有不同的抗原成分，因此基因组的重组可以产生以前从未存在的流感菌株。因此，这种新的重新分类病毒可能会引起流感流行病，并可能导致全球范围内约3亿人死亡。由于发病率，医疗保健和埋葬死者而导致的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的细胞或动物共同感染中生成这种保养病毒的方法，因此必须理解流感可能成为重要的生物武器。当前技术生产流感疫苗的另一个问题是，依赖使用时间耗时的胚胎卵（花了四个月），生产率较低，最麻烦的是，在需要用某些禽流感成分的疫苗时，无法使用。我们的目标是设计，构建和评估一种新型廉价的迅速修改的疫苗，用于无针头疫苗接种，以提供DNA疫苗和保护性抗原/表位，以诱导包括粘膜免疫，包括儿童和成人在内的保护性免疫，以防止流感和人类抗原抗原抗原抗原的疫苗感染。除了依赖于抗原抗原的保护性免疫外，我们还将通过递送含有T细胞表位的保守抗原来诱导更长的持久跨保护细胞免疫的潜力。该疫苗输送系统采用具有特殊新开发的特征的衰减沙门氏菌菌株来最大化淋巴组织的定殖，并且在体内表型中显示了受调节的延迟裂解，以释放编码宿主细胞和保护性抗原抗原和其他组织胞质胞质的流感型血瓜蛋白抗原的DNA疫苗。