Measuring Influenza and H1N1 vaccine responses in immunodeficient patients

测量免疫缺陷患者的流感和 H1N1 疫苗反应

基本信息

批准号：
8306395
负责人：
PAUL JOSEPH UTZ
金额：
$ 22.7万
依托单位：
STANFORD 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：
2011-07-18 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306395
关键词：
Adult Adverse event Algorithms Antibodies Antibody Formation Antibody Repertoire Antigens Autoantibodies Autoantigens Autoimmune Diseases Autoimmunity B-Lymphocytes Bioinformatics Biological Assay Blood Cells Blood specimen Cell Count Cellular biology Cessation of life Childhood Clinic Clinical Color Common Variable Immunodeficiency Coupled Custom DNA Databases Defect Disease Enrollment Epitopes Fire - disasters Future Genetic Polymorphism Genomics Glass Glucocorticoids Goals H1N1 vaccine Haplotypes Health Histones Human Immune Immune System Diseases Immune response Immune system Immunity Immunocompromised Host Immunoglobulin G Immunoglobulin M Immunologic Deficiency Syndromes Immunologic Receptors Immunologics Immunosuppressive Agents Individual Infection Influenza Inherited Instruction Interferon Type I Interferon-alpha Measurement Measures Memory B-Lymphocyte Microscope Monoclonal Antibodies Pathogenesis Patients Peptides Pharmaceutical Preparations Phenotype Plasma Plasmablast Post-Translational Protein Processing Prednisone Printing Proteome Protocols documentation RNA Rheumatism Sampling Sampling Studies Serum Severity of illness Signal Transduction Single Nucleotide Polymorphism Slide Solid Streptavidin Study Subject Subgroup Systemic Lupus Erythematosus T cell response T-Lymphocyte Testing Therapeutic immunosuppression Time Transcript Vaccinated Vaccination Vaccine Design Vaccines Virus acquired immunodeficiency base chemokine clinical phenotype cohort cytokine disease registry human subject immune function immunosuppressed improved influenza virus vaccine influenzavirus microbial mouse model nonhuman primate pathogen polyclonal antibody repository response seasonal influenza vaccination strategy

项目摘要

The goal of Project 3 is to comprehensively characterize immune systems of patients who are known to have abnormal immune systems, and to compare their immune responses with those of normal subjects. We will challenge the immune system by vaccinating patients with influenza vaccines, characterizing the response of an abnormal immune system to this perturbation. Project 3 will study patients with Common Variable Immunodeficiency Disease (CVID) and Systemic Lupus Erythematosus (SLE), prototypic diseases of immune dysregulation. There are 3 aims: (i.) to develop and validate a multistrain influenza and HINIv antigen microarray for profiling antibodies in vaccinated human subjects. We will clone and express major antigens from influenza strains, which will then be printed onto derivatized glass microscope slides. Arrays will first be validated using commercially-available monoclonal and polyclonal antibodies, then further validated using serum derived from normal subjects vaccinated with HINIv and seasonal flu vaccines; (ii.) to compare the baseline function of the immune system in normal human subjects with the baseline function of the immune system in immunosuppressed patients. We will create a comprehensive database of immune function measurements in CVID and in SLE, comparing the responses with normal subjects (Core C), and vaccinated subjects studied in Projects 1-7. We will take advantage of the Stanford Immunologic and Rheumatic Disease Registry and Biospecimen Repository, and the Adult and Pediatric Immunodeficiency Clinics for access to clinical samples, (iii.) to compare the global response of the immune system in normal subjects with the response in immunosuppressed patients (CVID, mild vs severe SLE, and therapeutic immunosuppression) when immunized with seasonal and HINIv influenza vaccines. We will test the hypothesis that a subset of healthy individuals has immune deflcit(s) similar to those observed in patients with autoimmunity, immunodeficiency disorders, or who are immunosuppressed with drugs such as glucocorticoids. We further hypothesize that this subset of patients will have an abnormal response to vaccine challenge with HI Nl v or seasonal flu vaccines. Results of Project 3 may improve future vaccination strategies for patients with immune deficiencies, and may identify subsets of "normal" patients who are unlikely to respond to existing vaccine protocols.

项目 3 的目标是全面描述已知患有以下疾病的患者的免疫系统特征：异常的免疫系统，并将其免疫反应与正常受试者的免疫反应进行比较。我们将通过给患者接种流感疫苗来挑战免疫系统，表征流感疫苗的反应对这种扰动的免疫系统异常。项目 3 将研究具有共同变量的患者免疫缺陷病（CVID）和系统性红斑狼疮（SLE），典型疾病免疫失调。有 3 个目标：(i.) 开发和验证多毒株流感和 HINIv 抗原微阵列，用于分析已接种疫苗的人类受试者的抗体。我们将克隆并表达主要来自流感病毒株的抗原，然后将其打印到衍生的玻璃显微镜载玻片上。数组首先使用市售的单克隆和多克隆抗体进行验证，然后进一步使用来自接种 HINIv 和季节性流感疫苗的正常受试者的血清进行验证；（二）到将正常人类受试者免疫系统的基线功能与免疫抑制患者的免疫系统。我们将创建一个全面的免疫数据库 CVID 和 SLE 中的功能测量，将反应与正常受试者进行比较（核心 C），以及项目 1-7 中研究的已接种疫苗的受试者。我们将利用斯坦福大学免疫学和风湿病登记和生物样本库，以及成人和儿童免疫缺陷诊所获取临床样本，(iii.) 比较正常情况下免疫系统的整体反应对免疫抑制患者有反应的受试者（CVID、轻度与重度 SLE 以及治疗性红斑狼疮）免疫抑制）当接种季节性流感疫苗和 HINIv 流感疫苗时。我们将测试假设健康个体的子集具有与患者中观察到的类似的免疫缺陷患有自身免疫性疾病、免疫缺陷疾病或使用以下药物抑制免疫的人糖皮质激素。我们进一步假设这部分患者会对以下药物产生异常反应：使用 HI Nl v 或季节性流感疫苗进行疫苗攻击。项目 3 的结果可能会改善未来的疫苗接种针对免疫缺陷患者的策略，并可能识别出“正常”患者的子集不太可能对现有的疫苗方案做出反应。