Measuring Influenza and H1N1 vaccine responses in immunodeficient patients

项目3的目标是全面表征已知患有免疫缺陷的患者的免疫系统。 异常的免疫系统，并将其免疫反应与正常受试者进行比较。我们将 通过给患者接种流感疫苗来挑战免疫系统， 异常的免疫系统来抵抗这种干扰项目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）， 免疫失调有三个目标：（一）开发和验证多株流感病毒和HINIV 抗原微阵列，用于分析接种疫苗的人类受试者中的抗体。我们将克隆并表达梅杰 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。阵列 将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 使用源自接种HINIV和季节性流感疫苗的正常受试者的血清进行验证;（ii.）到 将正常人受试者中免疫系统的基线功能与 免疫抑制患者的免疫系统。我们将建立一个全面的免疫数据库， CVID和SLE中的功能测量，与正常受试者的反应进行比较（核心C），以及 在项目1-7中研究的疫苗接种受试者。我们将利用斯坦福大学免疫学和 风湿病登记和生物标本库，成人和儿童免疫缺陷 获取临床样本的诊所，（iii.）来比较正常情况下， 免疫抑制患者（CVID、轻度vs重度SLE和治疗性SLE）中有应答的受试者 免疫抑制），当用季节性和HINIV流感疫苗免疫时。我们将测试 假设健康个体的一个子集具有与在患者中观察到的相似的免疫偏转 患有自身免疫、免疫缺陷疾病，或使用药物（如 糖皮质激素我们进一步假设，这部分患者将有一个异常的反应， 用HI NIV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 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产生反应。

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.