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Core C: Humoral and Serological Core

核心 C：体液和血清学核心

基本信息

批准号：
10180873
负责人：
Scott Eric Hensley
金额：
$ 17.96万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-08 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10180873
关键词：
Address Adult Affect Affinity Antibodies Antibody Response Antiviral Agents B-Lymphocytes B-cell receptor repertoire sequencing Binding Biological Assay Cancer Patient Childhood Acute Lymphocytic Leukemia Clinical Complex Cytomegalovirus Data Data Set Drug Targeting Enzyme-Linked Immunosorbent Assay Exposure to Flu virus Global Change Goals Health Hepatitis B Virus Hepatitis C Antibodies Hepatitis C virus Human Human Herpesvirus 4 Immune Immune response Immunity Immunoglobulin G Immunologics Immunomodulators Immunotherapy Individual Influenza Influenza vaccination Life Measurement Measures Memory Memory B-Lymphocyte PD-1 blockade Patients Peptides Sampling Serology Serology test Serum Services Specificity Standardization Techniques Technology Testing Thermometers Vaccines Viral Viral Antibodies Viral Antigens Virus anti-PD1 therapy anti-hepatitis B anti-influenza base chronic infection exposed human population flu influenzavirus innovation memory recall programmed cell death protein 1 response

项目摘要

Project Summary A major goal of this U19 is to determine how PD-1 blockade affects human antibody responses against different viral antigens. Core C will fully interrogate serum antibody responses against a range of different viruses from donors undergoing PD-1 therapy in Projects 1 and 2. The Core will standardize assays, complete assays, and provide computational support for the analyses of complex serological datasets. We will offer standardized ELISA-based services that quantify antibodies specific for 5 viruses that are relevant for Projects 1 and 2. We will also assess quality of antibody responses through ELISAs that measure relative affinities and isotype diversity. It is possible that PD-1 blockade affects antiviral antibody responses in more subtle or global ways. To address this, we will complete serological screens to examine how PD-1 blockade affects antibody responses to a large fraction of known human viruses. For this, we will use a new array-based assay, termed ‘Viroscan’, that measures antibody binding to >400,000 non-redundant viral peptides. We will also offer services that intensively analyze antibody responses against a single virus (influenza). All humans are exposed to influenza virus in childhood and all adult encounters with influenza involve both the recall of memory B cells and the stimulation of de novo B cell responses. Our influenza virus antigenic analyses will allow us to determine if PD-1 blockade differentially regulates de novo versus memory antibody responses. Together, these standardized services will allow for the complete antigenic characterization of serum samples for Projects 1 and 2.

项目摘要该U19的一个主要目标是确定PD-1阻断如何影响针对PD-I的人抗体应答。不同的病毒抗原核心C将针对一系列不同的血清抗体反应进行全面质询在项目1和2中，来自接受PD-1治疗的供体的病毒。核心将标准化分析，完成分析，并为复杂的血清学数据集的分析提供计算支持。我们将提供基于ELISA的标准化服务，量化与项目相关的5种病毒的特异性抗体 1和2.我们还将通过测定相对亲和力的ELISA评估抗体应答的质量，同种型多样性PD-1阻断可能以更微妙或更全面的方式影响抗病毒抗体应答。的方式为了解决这个问题，我们将完成血清学筛查，以检查PD-1阻断如何影响抗体对大部分已知的人类病毒的反应。为此，我们将使用一种新的基于阵列的检测方法，称为 “Virosan”，其测量抗体与> 400，000个非冗余病毒肽的结合。我们还将提供集中分析针对单一病毒（流感）的抗体反应的服务。所有的人类都是在儿童时期接触流感病毒和所有成年人接触流感都涉及回忆记忆B细胞和从头B细胞反应的刺激。我们的流感病毒抗原分析将允许我们确定PD-1阻断是否差异调节从头与记忆抗体应答。这些标准化服务将共同实现血清样本的完整抗原表征项目1和2。