Immune Responses Resource Core

免疫反应资源核心

• 批准号: 10460501
• 负责人: SABRA L. KLEIN
• 金额: $ 26.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460501
• 关键词: Age; Antibody Response; Antigens; Attention; B-Lymphocytes; Biological Assay; Cells; Core Facility; DNA Sequencing Facility; Data; Data Analyses; Disease; Enzyme-Linked Immunosorbent Assay; Exposure to; Flow Cytometry; Fostering; Gender; Gene Expression Profiling; Genes; Genetic; Genetic Transcription; Genomics; Genotype; Goals; Gonadal Steroid Hormones; Hemagglutinin; Human; Immune; Immune response; Immunity; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin M; Immunoglobulin Somatic Hypermutation; Immunologic Markers; Immunologics; Infection; Influenza; Influenza vaccination; Institution; Leadership; M2 protein; Measurement; Measures; Memory B-Lymphocyte; Mus; Neuraminidase; Pathway interactions; Phenotype; Plasmablast; Principal Investigator; Procedures; Protocols documentation; Reproducibility; Research; Research Personnel; Research Project Grants; Resources; Serology; Services; Sex Differences; Structure of germinal center of lymph node; Vaccination; Vaccine Antigen; Variant; Viral Antigens; Viral Proteins; age difference; deep sequencing; frailty; genomic data; immune function; improved; inflammatory marker; influenza virus vaccine; influenzavirus; interest; programs; response; sex; vaccine-induced antibodies

SEX AND AGE DIFFERENCES IN IMMUNITY TO INFLUENZA (SADII) IMMUNE RESPONSES RESOURCE CORE SUMMARY Under the leadership of Dr. Patricia Gearhart (Director) and Dr. Sabra Klein (Co-Director), the Immune Responses Core will provide the serological, cellular, and genetic assays that will be necessary for the accurate, and consistent measurement of sex and aged differences in immune responses to influenza vaccines and viral antigens. The Core will provide serological assessment of antibody responses to influenza vaccine and virus antigens for Research Projects 1, 2, and 3. The serological assessments will include microneutralization assays, hemagglutinin (HA) inhibition assays, and ELISAs to detect IgG that is specific for diverse influenza virus proteins, including HA, neuraminidase (NA), and the M2 protein as well as IgM and IgG isotypes to evaluate somatic hypermutation and class switching. The Core will also be responsible for conducting cellular analyses of antigen-specific (i.e., HA, NA, M2) B cells in humans and mice by flow cytometry using the MMI BD Immune Function Core facility. Particular attention will be paid to the quantification of plasmablasts and germinal center cells, including memory B cells and the recently characterized Age-associated B cells (ABCs). Finally, using the MMI Genomics and Analysis Sequencing Core, we will analyze the transcriptional variation associated with sex and age by transcriptional profiling antigen-specific B cells (i.e., plasmablasts) in humans and mice (Projects 1, 2, and 3). The transcriptional analyses will include using deep sequencing to quantify transcriptional activity in plasmablasts to evaluate the pathways differentially regulated by age and sex. Following repeated exposures to influenza antigens through infection and vaccination, an immune repertoire develops that reflects clonal selection during the primary response and recall and somatic rearrangement of VH genes following subsequent exposures, including following vaccination. V gene repertoires will be compared and analyzed for sex and age associated differences following vaccination. Together, the SADII Immune Responses Core will provide an in-depth analysis of how sex, age, and frailty alter antibody responses, B cell phenotypes, and B cell genotypes in response to influenza vaccination. With serological, cellular, and genomic assay capabilities, the SADII Immune Responses Resource Core can provide services to investigators interested in characterizing influenza virus-specific immune responses, which is currently not available at Johns Hopkins, and to SCOREs at other institutions that are seeking to measure inflammatory and immune markers of diverse diseases, beyond influenza.

性别和年龄差异对流感（SADII）免疫反应资源的免疫力差异 核心摘要 在Patricia Gearhart博士（主任）和Sabra Klein博士（联合导演）的领导下，免疫力 反应核心将提供血清学，细胞和遗传测定法 性别的准确且一致地测量性别和年龄差异对流感的免疫反应 疫苗和病毒抗原。核心将提供对流感抗体反应的血清学评估 研究项目1、2和3的疫苗和病毒抗原。血清学评估将包括 微中和化测定，血凝素（HA）抑制测定和ELISA检测特定于IgG的IgG 多种流感病毒蛋白，包括HA，神经氨酸酶（Na），M2蛋白以及IgM和IgG 同种型评估躯体超名和班级切换。核心也将负责 通过流动进行人类和小鼠的抗原特异性（即HA，Na，M2）B细胞的细胞分析 使用MMI BD免疫功能核心设施的细胞仪。特别关注 静脉内和生发中心细胞的定量，包括记忆B细胞和最近 表征与年龄相关的B细胞（ABC）。最后，使用MMI基因组学和分析测序 核心，我们将通过转录分析分析与性别和年龄相关的转录变化 人类和小鼠中的抗原特异性B细胞（即浆膜）（项目1、2和3）。转录 分析将包括使用深层测序来量化浆质中的转录活性以评估 通过年龄和性别差异地调节途径。通过反复暴露于流感抗原通过 感染和疫苗接种，一种免疫库发展，反映了主要的克隆选择 随后的暴露后，VH基因的反应和回忆和躯体重排，包括 疫苗接种后。 V将比较基因曲目并分析与性别相关的性别和年龄 疫苗接种后的差异。萨迪免疫反应核心将提供深入的核心 分析性别，年龄和脆弱的改变抗体反应，B细胞表型和B细胞基因型 对流感疫苗接种的反应。 Sadii具有血清学，细胞和基因组测定能力 免疫反应资源核心可以为有兴趣表征流感的调查人员提供服务 病毒特异性免疫反应，目前在约翰·霍普金斯（Johns Hopkins 试图衡量各种疾病的炎症和免疫标记的机构 流感。