Programming Long-lasting Immunity to Coronaviruses (PLUTO)

对冠状病毒进行持久免疫编程 (PLUTO)

基本信息

批准号：
10549475
负责人：
Ali Hassan Ellebedy
金额：
$ 250.69万
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/10549475
关键词：
2019-nCoV Achievement Address Affinity Animal Model Animals Antibodies Antibody Response Antigens Antiviral Agents B-Lymphocytes Binding Blood specimen Bone Marrow COVID-19 pandemic COVID-19 prevention COVID-19 vaccine Cessation of life Collaborations Coronavirus Coronavirus Infections Coronavirus spike protein Environment Epitopes Exposure to Ferrets Funding Future Generations Global Change Goals Hamsters Human Humoral Immunities Immune Immune response Immunity Immunology Individual Infection Institution Intervention Knowledge Messenger RNA Methods Modeling Molecular Monoclonal Antibodies Mus National Institute of Allergy and Infectious Disease Nucleosides Pathogenesis Persons Plasma Cells Pre-Clinical Model Public Health RNA vaccine Recombinants Recording of previous events Research Research Personnel Research Project Grants Resistance Resources Role SARS-CoV-2 B.1.617.2 SARS-CoV-2 variant Sarbecovirus Scientist Solid Specificity Specimen Structure Tissues Treatment Efficacy Vaccinated Vaccination Vaccine Design Vaccines Variant Viral World Health betacoronavirus betacoronavirus vaccine cell motility climate change clinical development coronavirus vaccination cross reactivity design draining lymph node efficacy evaluation efficacy testing future pandemic human model imprint influenzavirus lymph nodes member multidisciplinary neutralizing antibody new outbreak next generation novel pandemic coronavirus pandemic potential pandemic preparedness pathogenic virus prevent programs rational design response risk mitigation seasonal coronavirus structural biology success synergism universal coronavirus vaccine universal influenza vaccine universal vaccine vaccination strategy vaccine candidate vaccine development vaccine strategy virology zoonotic coronavirus

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大流行代表了一个特殊的公共卫生危机，强调了对更好的需求了解控制广泛保护的免疫调查并产生的机制候选疫苗候选者可以引起此类反应。计划项目标题为“编程长期编程对冠状病毒的免疫力（冥王星）”提出了一项全面的研究计划，以设计泛滥 SARBECOVIRUS和PAN-BETACORONAVIRUS疫苗，通过应用深入B细胞进行广泛保护在成功接种疫苗的冠状病毒免疫历史的背景下进行表征和/或感染。两个完整的研究项目将建立坚固，耐用的相关性并受保护的冠状病毒免疫力（项目1）以及病毒的设计和测试效率防变量泛 - 萨尔贝病毒和泛 - 贝曲霉病毒疫苗（项目2）。核心将与这两个研究项目旨在成功完成研究的目的。行政核心将管理财团，协调跨项目活动，并创建结构和实现冥王星目标所需的环境。抗体芯将形成大面板针对冠状病毒峰蛋白的重组单克隆抗体（mAb），以定义特异性和人类和动物引起的冠状病毒感染和/或疫苗接种引起的免疫复杂的呼吸型号。动物模型核心将提供批准，设施和专业知识的中心资源评估稳健前临床前的广泛交叉反应性冠状病毒抗体和疫苗的效率针对冠状病毒（包括精选剂）的模型。一个科学家的多学科团队来自五个具有出色工作记录的机构，将进行合作的记录拟议的研究。研究项目将相互合作，并与抗体和动物模型核心，由行政核心协调。集成和协同的活动跨项目和核心将推动该计划项目雄心勃勃的成功完成研究议程，实现了长期冥王星目标的实现 SARBECOVIRUS和PAN-BETACORONAVIRUS疫苗。这些发现将有助于遏制当前的SARS- COV-2大流行并减轻冠状病毒未来大流行的风险。