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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的目标是全面表征已知患有的患者的免疫系统