Antibody Core

抗体核心

基本信息

批准号：
10549477
负责人：
Ali Hassan Ellebedy
金额：
$ 20.85万
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：
2023
资助国家：
美国
起止时间：
2023-08-21 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10549477
关键词：
2019-nCoV Acceleration Achievement Activities of Daily Living Animal Model Antibodies Antigens B-Lymphocytes Bacillus anthracis Binding Blood Bone Marrow COVID-19 COVID-19 pandemic COVID-19 therapeutics Cell Separation Chronic Circulation Clinical Clinical Trials Clostridium difficile Collaborations Coronavirus Coronavirus Infections Coronavirus spike protein Development Diagnostic tests Dose Enterotoxins Environment Epitope Mapping Epitopes FDA approved Generations Goals Human Humoral Immunities Immune Immune response Immunity Immunize Immunologics Infection Inflammatory Institution Knowledge Life Malignant Neoplasms Maps Metabolic Diseases Methodology Middle East Respiratory Syndrome Coronavirus Moderna COVID-19 vaccine Monoclonal Antibodies Mus Neurons Nucleosides Peripheral Blood Mononuclear Cell Pfizer-BioNTech COVID-19 vaccine Pharmaceutical Preparations Pre-Clinical Model Productivity Proteins Public Health Publishing RNA vaccination RNA vaccine Recombinants Recording of previous events Research Research Project Grants Resources Respiratory syncytial virus SARS coronavirus SARS-CoV-2 antibody SARS-CoV-2 spike protein SARS-CoV-2 variant Sarbecovirus Scientist Screening procedure Specificity Specimen Structure Technology Therapeutic Time United States Universities Vaccination Vaccine Design Vaccinee Vaccines Variant Viral Virus Washington Work betacoronavirus betacoronavirus vaccine cohort coronavirus vaccination coronavirus vaccine cross reactivity design efficacy evaluation efficacy testing flexibility future pandemic human coronavirus human disease human model human monoclonal antibodies imprint improved insight lymph nodes multidisciplinary murine monoclonal antibody natural antibodies neutralizing antibody novel pathogenic microbe programs response risk mitigation single cell technology single-cell RNA sequencing synergism technology platform vaccine candidate vaccine development variants of concern ward

项目摘要

The SARS-CoV-2 pandemic represents an exceptional public health crisis highlighting the need for better understanding of the mechanisms controlling broadly protective immune responses and generating vaccine candidates able to elicit such responses. The program project entitled “Programming Long-lasting Immunity to Coronaviruses (PLUTO)” proposes a comprehensive research plan towards designing pan-sarbecovirus and pan-betacoronavirus vaccines with broad protection by applying in-depth B cell characterization in the context of coronavirus immune histories imprinted by successive vaccinations and/or infections. Two complementary research projects will establish correlates of robust, durable and protective coronavirus humoral immunity (Project 1) as well as design and test efficacy of viral variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines (Project 2). The Cores will synergize with the two research projects to support the successful completion of the research aims. The Administrative Core will manage the consortium, coordinate cross-project activities, and create the structure and environment needed to accomplish PLUTO’s goals. The Antibody Core will develop large panels of recombinant monoclonal antibodies (mAbs) against coronavirus spike proteins to define specificity and breath of immune responses elicited by coronavirus infections and/or vaccinations in humans and animal models. The Animal Model Core will provide a central resource with approvals, facilities, and expertise to assess efficacy of broadly cross-reactive coronavirus antibodies and vaccines in robust pre-clinical models against a spectrum of coronaviruses, including Select Agents. A multidisciplinary team of scientists from five institutions who have an outstanding track record of working collaboratively will conduct the proposed studies. The Research Projects will collaborate with each other and with the Antibody and Animal Model Cores, coordinated by the Administrative Core. The integrated and synergistic activities across Projects and Cores will drive the successful completion of the program project’s ambitious research agenda, enabling achievement of the long-term PLUTO goal of developing variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines. These findings will contribute to curbing the current SARS-CoV-2 pandemic and mitigate the risk of future pandemics with coronaviruses.

SARS-CoV-2 大流行代表了一场特殊的公共卫生危机，凸显了需要采取更好的措施了解控制广泛保护性免疫反应和生产疫苗的机制候选人能够引起这样的反应。冠状病毒（PLUTO）”提出了设计泛冠状病毒的综合研究计划通过应用深入的 B 细胞表征，开发出具有广泛保护作用的泛 β 冠状病毒疫苗连续接种疫苗和/或感染所留下的冠状病毒免疫史的背景。补充研究项目将建立强大、持久和保护性冠状病毒的相关性体液免疫（项目1）以及抗病毒变异泛沙病毒和病毒的设计和测试功效泛β冠状病毒疫苗（项目2）将与两个研究项目协同支持。行政核心将管理该联盟，以成功完成研究目标。协调跨项目活动，并创建完成 PLUTO 所需的结构和环境抗体核心将开发大量重组单克隆抗体 (mAb)。冠状病毒刺突蛋白定义冠状病毒引起的免疫反应的特异性和呼吸人类和动物模型中的感染和/或疫苗接种将提供一个中心。拥有批准、设施和专业知识的资源，可评估广泛交叉反应的冠状病毒的功效针对一系列冠状病毒（包括 Select）的强大临床前模型中的抗体和疫苗代理人由来自五个机构的多学科科学家组成，他们在以下方面拥有杰出的记录。研究项目将与各方合作开展拟议的研究。其他以及抗体和动物模型核心，由行政核心协调。跨项目和核心的综合和协同活动将推动项目的成功完成计划项目雄心勃勃的研究议程，能够实现 PLUTO 的长期目标这些发现将有助于开发防变异的泛 sarbecovirus 和泛 betacoronavirus 疫苗。遏制当前的 SARS-CoV-2 大流行并降低未来冠状病毒大流行的风险。