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Salmonella anti-influenza DNA & antigen delivery vaccine

沙门氏菌抗流感DNA

基本信息

批准号：
7342503
负责人：
ROY CURTISS III
金额：
$ 59.06万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-16 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7342503
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

项目摘要

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（由申请方提供）：流感病毒显示抗原漂移，因此每年需要开发更新的疫苗。错误判断或缺乏适当的信息可能导致疫苗的设计和生产对流行毒株的保护能力有限。流感病毒也通过两种不同流感病毒共感染动物宿主细胞而经历基因组重排。由于存在感染鸟类、猪、马和人类的流感毒株，并且由于这些适应宿主的病毒具有不同的抗原组分，基因组重配可以产生以前从未存在过的流感毒株。因此，这种新的重组病毒可能导致流感大流行，有可能导致全球约3亿人死亡。这种流行病由于发病率、保健提供和埋葬死者而造成的经济后果将是惊人的。由于存在在实验室中或通过故意共感染细胞或动物来产生这种重配病毒的方法，因此必须认识到流感可能成为重要的生物武器。目前制造流感疫苗的技术的另一个问题是依赖于使用含胚蛋，这是耗时的（需要四个月），具有低生产率，并且最麻烦的是，当需要制造具有一些禽流感组分的疫苗时不能使用。我们的目标是设计、构建和评估一种新型廉价的快速修饰疫苗，用于口服无针接种，以递送DNA疫苗和保护性抗原/表位，从而在儿童和成人中诱导保护性免疫，包括粘膜免疫，以预防具有禽类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，我们还将彻底研究通过递送含有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潜力。疫苗递送系统采用具有特殊新开发特征的减毒沙门氏菌菌株，以最大限度地增加淋巴组织的定植，并显示出受调节的体内延迟溶解表型，以在宿主细胞的胞质溶胶中释放编码流感血凝素抗原的DNA疫苗，并将保护性抗原/表位递送到其他组织。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype.

DOI：
10.1016/j.vaccine.2010.07.083
发表时间：
2010-09-24
期刊：
VACCINE
影响因子：
5.5
作者：
Ameiss, Keith;Ashraf, Shamaila;Kong, Wei;Pekosz, Andrew;Wu, Wai-Hong;Milich, David;Billaud, Jean-Noel;Curtiss, Roy, III
通讯作者：
Curtiss, Roy, III

Generation of influenza virus from avian cells infected by Salmonella carrying the viral genome.