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Monoclonal Antibody Technology Core

单克隆抗体技术核心

基本信息

批准号：
10223126
负责人：
Patrick Christopher Wilson
金额：
$ 40.5万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10223126
关键词：
Affinity Antibodies Antibody Formation Antibody Response Antibody-mediated protection Antigens B-Lymphocytes Binding Cell surface Cells Collaborations Communities Data Epitopes Ferrets Frequencies Funding Goals Hemagglutinin Immunity Immunoglobulin Genes Individual Infection Influenza Influenza B Virus Influenza Hemagglutinin Influenza Therapeutic Influenza vaccination Laboratories Learning Monoclonal Antibodies Mus Mutation Neuraminidase Nuclear Protein Patients Plasma Cells Plasmablast Population Proteins Reagent Research Resources Services Source Specificity Structure of germinal center of lymph node Technology Testing Therapeutic Thinking Update Vaccinated Vaccine Design Vaccine Production Vaccines Viral Viral Proteins Virus Zoonoses aged anti-influenza base cohort design improved in vivo influenza infection influenza virus strain influenza virus vaccine insight interest monoclonal antibody production mutant novel novel vaccines pandemic disease programs protective efficacy response therapeutic target universal influenza vaccine vaccine candidate vaccine efficacy vaccine trial

项目摘要

Summary Improving the durability and efficacy of the antibody response induced by novel influenza vaccines, and generating novel anti-influenza therapeutic reagents are central goals of influenza research. A more durable influenza vaccine and broad-spectrum therapeutics are important for protection against mutant and novel influenza strains that cause annual infection and pandemics. Monoclonal antibodies (mAbs) have provided major advances both in our thinking and for design of more broadly-protective vaccines and as potential broad- spectrum anti-influenza therapeutics. While hemagglutinin (HA) remains a mainstay as a vaccine or therapeutic target, antibodies to neuraminidase (NA) and other influenza proteins are much less studied but are also protective and may bind a wider range of influenza strains. In the various projects of this program mAbs against influenza HA, NA, matrix protein (M1) and nuclear protein (NP) will be used to identify epitopes, to evaluate known and novel epitopes for breadth and potency of protection, to learn new mechanisms of protection, and to evaluate trial vaccine efficacy. Thus the four projects in this program will use the mAb core as a central resource in order to inform on antigen and vaccine design. Further, the studies proposed will generate large panels of mAbs that may themselves be valuable as therapeutic reagents to treat influenza infections. For this we will produce antibodies from novel cohorts that we have identified that preferentially target conserved epitopes on HA, and at substantially greater frequencies to conserved epitopes on other influenza proteins including NA, NP and M1. The core will also help the projects evaluate trial vaccine efficacy and specificity at the monoclonal antibody level.

总结改善新型流感疫苗诱导的抗体应答的持久性和效力，以及产生新的抗流感治疗试剂是流感研究的中心目标。更耐用的流感疫苗和广谱治疗剂对于针对突变体和新引起每年一次的感染和大流行的流感病毒株。单克隆抗体（mAb）提供了在我们的思维和设计更广泛的保护疫苗方面取得了重大进展，广谱抗流感治疗剂。虽然血凝素（HA）仍然是作为疫苗的主要成分，治疗靶点，神经氨酸酶（NA）和其他流感蛋白的抗体研究得少得多，也具有保护性，可以结合更广泛的流感病毒株。在这个项目的各个项目中抗流感HA、NA、基质蛋白（M1）和核蛋白（NP）的mAb将用于鉴定表位，评估已知和新的表位的保护范围和效力，学习新的机制，保护，并评估试验疫苗的有效性。因此，该计划中的四个项目将使用mAb核心作为一个中心资源，以便为抗原和疫苗设计提供信息。此外，拟议的研究将产生大量单克隆抗体，这些单克隆抗体本身可能作为治疗流感的治疗试剂是有价值的感染.为此，我们将从我们已经确定的新队列中产生抗体，靶向HA上的保守表位，并以显著更高的频率靶向其他HA上的保守表位。流感蛋白包括NA、NP和M1。核心还将帮助项目评估试验疫苗的有效性和单克隆抗体水平的特异性。