Monoclonal Antibody Technology Core

单克隆抗体技术核心

• 批准号: 10468074
• 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
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468074
• 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; Persons; Plasma Cells; Plasmablast; Population; Proteins; Reagent; Research; Resources; Services; Source; Specificity; Structure of germinal center of lymph node; Technology; Testing; Therapeutic; Thinking; Update; Vaccine Design; Vaccinee; 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

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.

概括 提高新型流感疫苗诱导的抗体反应的持久性和有效性，以及 产生新型抗流感治疗试剂是流感研究的中心目标。更耐用 流感疫苗和广谱疗法对于预防突变和新型流感非常重要 引起年度感染和大流行的流感病毒株。单克隆抗体 (mAb) 提供了 我们的思想和设计更广泛的保护性疫苗方面取得了重大进展，并且具有潜在的广泛性 谱抗流感疗法。虽然血凝素 (HA) 仍然是疫苗或药物的支柱 治疗靶标、神经氨酸酶 (NA) 抗体和其他流感蛋白的研究要少得多，但 还具有保护作用，可以结合更广泛的流感病毒株。在本计划的各个项目中 针对流感 HA、NA、基质蛋白 (M1) 和核蛋白 (NP) 的单克隆抗体将用于鉴定表位， 评估已知和新颖表位的保护广度和效力，了解新的机制 保护，并评估试验疫苗的功效。因此，该计划中的四个项目将使用 mAb 核心 作为提供抗原和疫苗设计信息的中心资源。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很有价值 感染。为此，我们将从我们已确定的新群体中优先生产抗体 靶向HA上的保守表位，并且以更高的频率靶向其他上的保守表位 流感蛋白包括NA、NP和M1。该核心还将帮助项目评估试验疫苗的功效 和单克隆抗体水平的特异性。