Human Monoclonal Antibodies

人单克隆抗体

基本信息

批准号：
7696520
负责人：
Patrick Christopher Wilson
金额：
$ 55.55万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7696520
关键词：
Acute Address Admission activity Adverse event Affinity Agonist Anthrax Vaccines Antibodies Antibody Formation Antibody Specificity Antibody-Dependent Enhancement Antigens Award B cell differentiation B cell repertoire B-Cell Activation B-Cell Development B-Lymphocytes Binding Biological Assay Biological Warfare Biology Blood Blood Vessels Blood specimen Cell Separation Cell physiology Cells Chicago Child Clinical Clinical Trials Clonality Cloning Collaborations Communicable Diseases Complement component C1s Convalescence Cross-Sectional Studies Data Dengue Dengue Hemorrhagic Fever Dengue Shock Syndrome Dengue Virus Development Diagnosis Diagnostic Emerging Communicable Diseases Epitopes Equilibrium Evaluation Event Fc Receptor Flavivirus Flow Cytometry Freezing Funding Future Generations Genes Genus Capra Goals Hospitals Human Humoral Immunities Immune Immune response Immune system Immunity Immunoglobulin G Immunoglobulin Genes Immunoglobulin M Immunoglobulin Somatic Hypermutation Immunology In Vitro Incidence Individual Infection Infectious Agent Kinetics Laboratories Lead Learning Libraries Life Link Literature Longitudinal Studies Memory Memory B-Lymphocyte Methods Modeling Molecular Monoclonal Antibodies Mus Passive Immunization Pathology Pharmacologic Substance Phenotype Plasma Cells Plasmablast Population Process Production Protocols documentation Public Health Reaction Reagent Recording of previous events Reliance Research Infrastructure Reverse Transcriptase Polymerase Chain Reaction Role Sampling Secondary Immunization Serologic tests Serological Serotyping Serum Severity of illness Shipping Ships Somatic Mutation Sorting - Cell Movement Source Specificity Specimen Staging Structure of germinal center of lymph node Surveys Symptoms Syndrome Technology Testing Thailand Therapeutic Time Universities Vaccinated Vaccination Vaccine Antigen Vaccines Viral Viremia Virus Virus Diseases Yellow Fever Yellow fever virus aged anthrax toxin biodefense design enzyme linked immunospot assay fascinate human monoclonal antibodies humanized antibody in vivo influenzavirus long term memory longitudinal analysis monocyte mouse model neutralizing antibody new technology nonhuman primate novel pathogen receptor repository response secondary infection technology development tool vaccine-induced immunity volunteer

项目摘要

The isolation of antibodies directly from immune donors offers the advantage of fully exploiting the strength of the human antibody response to vaccination or infection. By following the developmental fate of antigenspecific B cell populations through analysis of their antibodies we can generate a direct survey of B cell function. In this competitive renewal of our Technology Development Project (TOP) on Human Monoclonal Antibodies we combine two uniquely powerful new technologies recently developed that for the first time allow the efficient analysis of human B cell specificity en mass. One approach pioneered by Dr. Lanzavecchia, provides an analysis of the entire history of B cell specificities by efficiently producing mAbs from the long-term memory B cell compartment. The second technology from the Wilson and Ahmed laboratories scrutinizes current, ongoing plasmablast specificities and generates large numbers of antigenspecific antibodies in a short time that are predominantly specific to the antigens. We will use these tools to address fundamental questions about the human B cell response to yellow fever virus (YFV) and dengue virus. By combining these powerful platforms of generating human mAbs (plasmablasts and memory B cells) we should be able to comprehensively analyze the human B cell response to these viruses and to probe the relationship between memory B cells and antibody secreting plasma cells. Because the antibodies produced are fully human they can yield valuable diagnostics and allow for safer Pharmaceuticals than chimeric or humanized antibodies. Thus, in addition to addressing these fundamental questions, our proposed studies should also result in the development of a large panel of human mAbs against YFV and dengue - two flaviviruses that are of important public health concern and are high priority biodefense pathogens. Three specific aims are proposed: 1) Characterize the primary human B cell response to YFV-17D leading to the generation of ASCs and long-term memory B cells; 2) Analyze the dynamics, variable gene repertoire, and the specificity of ASC and memory cells induced by booster vaccination with YFV-17D. 3) Characterize the human B cell response to acute dengue virus infection of Children.

直接从免疫供体中隔离抗体具有充分利用强度的优势人类抗体对疫苗接种或感染的反应。通过遵循抗原特异性的发育命运 B细胞种群通过分析其抗体，我们可以对B细胞进行直接调查功能。在我们的技术开发项目（TOP）的人类单克隆的竞争更新中抗体我们结合了两种独特功能强大的新技术最近首次开发了该技术允许对人类B细胞特异性的有效分析。博士开创的一种方法 Lanzavecchia，通过有效产生mAb来对B细胞特异性的整个历史进行分析来自长期记忆B细胞室。威尔逊和艾哈迈德的第二种技术实验室仔细检查了持续的浆质特异性，并产生大量抗原特异性抗体在短时间内主要是抗原特异的。我们将使用这些工具来解决有关人类B细胞对黄热病病毒（YFV）和登革热的基本问题病毒。通过结合这些强大的生成人物mab的平台（浆质和记忆B细胞）我们应该能够全面分析人类B细胞对这些病毒的反应并探测记忆B细胞与分泌浆细胞的抗体之间的关系。因为产生的抗体是完全人类的药物比嵌合或人源化抗体。因此，除了解决这些基本问题，我们提出的研究还应导致大量人物板的发展反对YFV和登革热 - 两个具有重要公共卫生关注的黄病毒，优先考虑生物形式病原体。提出了三个具体目标：1）特征是主要的人类B细胞对YFV-17D的反应，导致ASC和长期记忆B细胞的产生； 2）分析动力学，可变基因库以及助推器诱导的ASC和记忆细胞的特异性 YFV-17D疫苗接种。 3）表征人类B细胞对急性登革热病毒感染的反应孩子们。