IMMUNOLOGICAL MEMORY TO VACCINATION

疫苗接种的免疫记忆

基本信息

批准号：
7657620
负责人：
Rafi Ahmed
金额：
$ 53.73万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7657620
关键词：
2 year old Acute Address Adult Affect Agonist Anthrax Vaccines Anthrax disease Antibodies Antibody Formation Antigen Receptors Antigenic Specificity Antigens Antiviral Agents Antiviral Response Attenuated Live Virus Vaccine Attenuated Vaccines B cell differentiation B-Cell Activation B-Lymphocyte Subsets B-Lymphocytes Back Biological Assay Blood Bystander Effect CCR5 gene CD4 Positive T Lymphocytes CD8B1 gene Cell Communication Cell Count Cell Differentiation process Cell surface Cells Child Chronic Collaborations Condition Cross-Sectional Studies Cytomegalovirus Data Development Effector Cell Epitope Mapping Epitopes Gene Expression Gene Expression Profile Generations Genes Genomics Goals HIV Homing Human Human Herpesvirus 4 Immune Immune response Immune system Immunity Immunization Immunologic Memory Immunology In Vitro Individual Infection Kinetics Knowledge Label Laboratories Licensing Life Location Longitudinal Studies Lymphocyte Lymphocyte Activation Lymphocyte Count Lymphocyte Homing Receptors MHC Class I Genes Maintenance Maps Measles Measures Memory Memory B-Lymphocyte Modeling Molecular Molecular Profiling Monitor Mumps Mus Natural Immunity Nature Numbers Pathway interactions Pattern Peripheral Blood Mononuclear Cell Phase Phenotype Plasma Cells Play Poliomyelitis Population Process Production Proliferating Property Prospective Studies Proteome Proteomics Purpose Regulation Relative (related person)Research Resolution Resources Role Rubella SELL gene Sampling Serological Serum Staining method Stains System T memory cell T-Cell Activation T-Lymphocyte T-Lymphocyte Epitopes T-Lymphocyte Subsets Techniques Tetanus Toxoid Time Tissues Treatment Protocols Up-Regulation Vaccinated Vaccination Vaccines Viral Vaccines Virus Virus Diseases Water Week Yellow Fever Virus Infection Yellow fever virus aluminum sulfate anthrax protective factor base biodefense cytokine cytotoxicity day design enzyme linked immunospot assay improved in vivo influenzavirus insight interest killings long term memory lymph nodes mathematical model memory CD4 T lymphocyte mouse model programs research study response selective expression size vaccine efficacy volunteer

项目摘要

The goal of this proposal is to understand how a successful vaccine induces long-term immunological memory in humans. To achieve this goal we propose to conduct a detailed cellular and molecular characterization of human immune responses induced by the yellow fever virus (YFV) vaccine. This is one of our most efficacious vaccines and induces long-term immunity that lasts for decades. Also, since YFV- 17D is a live attenuated vaccine and most of the U.S. population is not exposed to YFV, this provides a unique opportunity to analyze antiviral responses in humans during the course of a primary infection and then to monitor the generation and maintenance of immune memory after resolution of the infection. One of the potential benefits of understanding how a successful vaccine induces long-term memory is that this knowledge can be applied to improving other less effective vaccines. Such a comparison could define the signatures of a "good" versus "bad" vaccine and provide a rational basis for improving vaccine efficacy. To address this issue, we will examine human immune responses induced by the anthrax vaccine. We have chosen to study the anthrax vaccine because of the obvious importance of anthrax in biodefense-related research and also because there is clearly a need for a better anthrax vaccine. However, prior to designing strategies for improving the anthrax vaccine, it is first essential to better characterize the magnitude and quality of the immune responses induced in humans by the currently licensed anthrax vaccine. The specific aims of this proposal are as follows: 1. To determine if there is an early global sensitization of na'fve T and B cells after immunization and to see if this correlates with the magnitude and duration of the adaptive immune response. 2. To characterize the primary and memory T cell responses to YFV and anthrax vaccine. 3. To define the molecular and functional profile of memory T cell differentiation in vivo following an acute viral infection and to examine how the strength and duration of T cell stimulation effects memory differentiation. 4. To examine bystander effects on memory T cells during viral infection in humans. 5. To understand the mechanisms of long-term serological memory and to define the gene expression profiles of memory B cells.

该提案的目的是了解成功的疫苗如何诱导长期免疫学人类的记忆。为了实现此目标，我们建议进行详细的细胞和分子黄热病病毒（YFV）疫苗引起的人类免疫反应的表征。这是一个我们最有效的疫苗并诱导了持续数十年的长期免疫力。另外，由于yfv- 17D是一种现场衰减的疫苗，大多数美国人口不暴露于YFV，这提供了在原发性感染过程中，分析人类抗病毒药反应的独特机会然后监测感染分辨率后免疫记忆的产生和维护。之一了解成功疫苗如何引起长期记忆的潜在好处是知识可以应用于改善其他有效较低的疫苗。这样的比较可以定义 “好”与“坏”疫苗的特征，并为提高疫苗功效提供了合理的基础。到解决这个问题，我们将检查炭疽疫苗引起的人类免疫反应。我们有选择研究炭疽疫苗，因为炭疽在生物浮雕有关研究，还因为显然需要更好的炭疽疫苗。但是，在设计之前改善炭疽疫苗的策略，首先要更好地表征大小和当前许可的炭疽疫苗在人类引起的免疫反应的质量。具体该提议的目的如下：1。确定na'fve t和b是否有早期的全球敏感性免疫后细胞，看看这是否与适应性免疫的大小和持续时间相关回复。 2。表征对YFV和炭疽疫苗的主要和内存T细胞反应。 3 在急性病毒后定义体内记忆T细胞分化的分子和功能谱感染并检查T细胞刺激的强度和持续时间如何影响记忆分化。 4。检查人类病毒感染期间对记忆T细胞的影响。 5。了解长期血清学记忆的机制，并定义记忆B细胞的基因表达谱。