Novel Vaccination Strategies Against Epidemic and Pandemic Influenza Viruses to I

针对流行性和大流行性流感病毒的新疫苗接种策略

基本信息

批准号：
8318807
负责人：
MURALI KRISHNA KAJA
金额：
$ 38.36万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8318807
关键词：
Address Adenovirus Vector Adjuvant Adoptive Cell Transfers Adult Affect Age Aging Antigens Avian Influenza Avian Influenza A Virus B-Lymphocytes Binding Birds Bone Marrow Categories Cells Cessation of life Chimera organism Clinical Trials Clonal Expansion Data Defect Disease Dose Double-Stranded RNA Elderly Epidemic Event Fright Generations Goals Grant Health Human Immune Immune response Immune system Immunity Individual Infection Inflammatory Inflammatory Response Influenza Influenza A Virus, H5N1 Subtype Influenza A virus Influenza vaccination Interferon Type I Interferons Investigation Knockout Mice Knowledge Laboratories Link Mediating Memory Modeling Mus National Institute of Allergy and Infectious Disease Polymerase Population Predisposition Production Proteins Public Health Publishing RNA Reagent Respiratory Tract Infections Role Signal Induction Signal Pathway Signal Transduction Stimulus System T-Lymphocyte Techniques Testing Time Transgenic Organisms United States Vaccinated Vaccination Vaccines Viral Virulent Virus adaptive immunity age related aged aluminum sulfate base cellular targeting clinically relevant design egg fitness follow-up immunogenicity improved in vivo influenza virus vaccine influenzavirus meetings mortality novel pandemic disease pandemic influenza pathogen prevent programs research study respiratory response sensor success targeted delivery tripolyphosphate vaccination strategy young adult

项目摘要

DESCRIPTION (provided by applicant): Influenza is both a major public health threat and a NIAID bio defense category C priority pathogen. About 36,000 people die every year in the United States alone due to infection with commonly circulating influenza A viruses. Nearly 90% of these deaths are in elderly people. These deaths occur despite the fact that current influenza vaccines reach >65% of the adult population. Moreover, highly pathogenic avian H5N1 viruses cause 60% mortality in infected individuals. It is feared that a pandemic can happen at any time. Thus, there is an urgent need for an understanding of factors that influence induction of optimal influenza immunity, and for developing novel vaccination strategies that can elicit better protective immunity. These strategies should consider the age-mediated heightened susceptibility to influenza. The long-term objective of this proposal, therefore, is to both improve current vaccination strategies and contribute to the design of novel vaccination strategies to control epidemic and pandemic influenza viruses with particular regard to the elderly population. We hypothesize that age mediated effects in type-I interferon (IFN-I) induction/signaling combined with viral IFN-I evasive strategies may adversely affect influenza- specific protective immunity. This proposal tests this hypothesis and explores novel vaccination strategies for inducing RIG-I mediated type-I interferon signaling pathways during priming as means of inducing enhanced protective immunity against influenza viruses. Aim 1 examines whether age- dependent defects to influenza immunization can be minimized by interfering with viral IFN-I evasive strategies, Aim 2 tests the contribution of IFN-I signals on cells of innate immune system in generating influenza specific adaptive response, Aim 3 examines the effect of enhanced IFN-I signaling during priming on influenza-specific memory fitness, and Aim 4, explores novel vaccination strategies that enhance RIG-I mediated type-I interferon signals during priming to increase the immunogenicity, durability, and protective ability of immune response. Human epidemic and pandemic avian influenza strains will be tested in the well-characterized respiratory infection models in mice using cutting edge reagents/techniques such as TCR transgenic, knockout mice, adoptive cell transfers, bone marrow chimeras, and MHC tetramers. This knowledge not only contributes to improved vaccination strategies against influenza, especially in elderly, but also has implications for novel vaccination strategies against a variety of diseases. PUBLIC HEALTH RELEVANCE: The long-term objectives of this proposal are to design novel and improved vaccination strategies to control epidemic and pandemic influenza viruses. This knowledge will not only contribute to improved vaccination strategies against influenza, especially in elderly, but also has implications for novel vaccination strategies against a variety of diseases.

描述（由申请人提供）：流感既是主要的公共卫生威胁，也是 NIAID 生物防御 C 类优先病原体。仅在美国，每年就有约 36,000 人因感染常见的甲型流感病毒而死亡。其中近 90% 的死亡是老年人。尽管目前的流感疫苗覆盖了超过 65% 的成年人口，但这些死亡还是发生。此外，高致病性禽 H5N1 病毒导致感染者 60% 的死亡率。人们担心大流行随时可能发生。因此，迫切需要了解影响最佳流感免疫力诱导的因素，并开发能够引发更好保护性免疫力的新型疫苗接种策略。这些策略应考虑年龄介导的流感易感性增加。因此，该提案的长期目标是改进当前的疫苗接种策略，并有助于设计新的疫苗接种策略以控制流行性和大流行性流感病毒，特别是针对老年人群。我们假设年龄介导的 I 型干扰素 (IFN-I) 诱导/信号传导效应与病毒 IFN-I 规避策略相结合可能会对流感特异性保护性免疫产生不利影响。该提案测试了这一假设，并探索了在启动过程中诱导 RIG-I 介导的 I 型干扰素信号通路的新疫苗接种策略，作为诱导增强针对流感病毒的保护性免疫力的手段。目标 1 检查是否可以通过干扰病毒 IFN-I 逃避策略来最大程度地减少流感免疫的年龄依赖性缺陷，目标 2 测试 IFN-I 信号对先天免疫系统细胞产生流感特异性适应性反应的贡献，目标 3 检查启动期间增强的 IFN-I 信号对流感特异性记忆适应性的影响，以及目标 4，探索了在启动期间增强 RIG-I 介导的 I 型干扰素信号的新疫苗接种策略启动以增加免疫反应的免疫原性、持久性和保护能力。将使用 TCR 转基因、基因敲除小鼠、过继细胞移植、骨髓嵌合体和 MHC 四聚体等尖端试剂/技术，在小鼠呼吸道感染模型中测试人类流行性和大流行性禽流感毒株。这些知识不仅有助于改进流感疫苗接种策略，尤其是老年人的疫苗接种策略，而且对针对多种疾病的新型疫苗接种策略也具有影响。公共卫生相关性：该提案的长期目标是设计新颖且改进的疫苗接种策略来控制流行性和大流行性流感病毒。这些知识不仅有助于改进流感疫苗接种策略，尤其是老年人的疫苗接种策略，而且还对针对多种疾病的新疫苗接种策略具有影响。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8(+) T cell responses in mice.

即时疫苗：生物矿化磷酸钙核心-免疫原外壳纳米颗粒可在小鼠体内诱导持久的 CD8( ) T 细胞反应。

DOI：
10.1016/j.nano.2013.11.007
发表时间：
2014-04
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
5.4
作者：
Zhou, Weibin;Moguche, Albanus O.;Chiu, David;Murali-Krishna, Kaja;Baneyx, Francois
通讯作者：
Baneyx, Francois