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。错误判断或缺乏适当信息可能导致疫苗设计和生产的疫苗抵御流行菌株的能力有限。流感还通过用两种不同的流感病毒共同感染动物宿主细胞来进行基因组重排。由于存在感染鸟类、猪、马和人类的流感病毒株，并且这些适应宿主的病毒具有不同的抗原成分，因此基因组重排可以产生以前从未存在过的流感病毒株。因此，此类新的重排病毒可能导致流感大流行，并可能导致全球约 3 亿人死亡。这种流行病由于发病率、医疗保健服务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细胞或动物的故意共同感染产生此类重配病毒的方法，因此必须认识到流感可能成为一种重要的生物武器。现有技术制造流感疫苗的另一个问题是依赖于使用含胚蛋，耗时长（需要四个月），生产率低，而且最麻烦的是，在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、构建和评估一种新型廉价快速可修改疫苗，用于口服无针疫苗接种，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，以预防流感病毒感染禽类和人类抗原成分。除了依赖于诱导针对 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。该疫苗递送系统采用具有新开发的特殊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，并表现出体内受调节的延迟裂解表型，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/表位递送至其他组织。

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.