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.

SADII免疫应答资源的性别和年龄差异 核心摘要 在Patricia Gearhart博士（主任）和Sabra Klein博士（联合主任）的领导下，免疫 反应核心将提供血清学，细胞和遗传分析，这将是必要的， 准确、一致地测量流感免疫应答的性别和年龄差异 疫苗和病毒抗原。核心将提供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 微量中和试验、血凝素（HA）抑制试验和ELISA，以检测特异于 多种流感病毒蛋白，包括HA、神经氨酸酶（NA）和M2蛋白以及IgM和IgG 同种型以评估体细胞超突变和类别转换。核心还将负责 进行抗原特异性的细胞分析（即，HA、NA、M2）B细胞 使用MMI BD免疫功能核心设施进行流式细胞术。将特别注意 定量浆母细胞和生殖中心细胞，包括记忆B细胞和最近的 特征性的树突状细胞相关B细胞（ABC）。最后，使用MMI基因组学和分析测序， 核心，我们将通过转录谱分析与性别和年龄相关的转录变异 抗原特异性B细胞（即，浆母细胞）在人类和小鼠（项目1，2和3）。转录 分析将包括使用深度测序来量化浆母细胞中的转录活性，以评估 受年龄和性别差异调节的途径。在反复暴露于流感抗原后， 感染和疫苗接种后，免疫库的发展反映了在初级免疫过程中的克隆选择。 随后暴露后VH基因的反应和回忆以及体细胞重排，包括 接种疫苗后。将比较和分析V基因组的性别和年龄相关性， 接种疫苗后的差异总之，SADII免疫反应核心将提供深入的 分析性别、年龄和虚弱如何改变抗体应答、B细胞表型和B细胞基因型， 接种流感疫苗的反应。SADII具有血清学、细胞和基因组分析能力， 免疫反应资源中心可以为对流感特征感兴趣的研究人员提供服务 病毒特异性免疫反应，这是目前还没有在约翰霍普金斯，并在其他SCORE 这些机构正在寻求测量各种疾病的炎症和免疫标志物， 流感。