Programming Long-lasting Immunity to Coronaviruses (PLUTO)

对冠状病毒进行持久免疫编程 (PLUTO)

• 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
• 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

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大流行是一场特殊的公共卫生危机，突出表明需要更好地 了解广泛控制保护性免疫反应的机制， 能够引起这种反应的候选疫苗。题为“持久方案拟订”的方案项目 免疫冠状病毒（PLUTO）”提出了一个全面的研究计划，旨在设计泛- 通过应用深层B细胞具有广泛保护的肉瘤病毒和泛β冠状病毒疫苗 在冠状病毒免疫历史背景下的连续疫苗接种特征 和/或感染。两个互补的研究项目将建立强大的，持久的 和保护性冠状病毒体液免疫（项目1）以及病毒的设计和测试功效 抗变异泛肉瘤病毒和泛β冠状病毒疫苗（项目2）。核心将与 两个研究项目，以支持研究目标的顺利完成。行政 核心将管理联合体，协调跨项目活动，并创建结构， 实现PLUTO目标所需的环境。抗体核心将开发大型面板， 针对冠状病毒刺突蛋白的重组单克隆抗体（mAb），以确定特异性， 冠状病毒感染和/或疫苗接种在人类和动物中引起的免疫反应的呼吸 模型动物模型中心将提供一个中心资源，包括批准、设施和专业知识。 评估广泛交叉反应的冠状病毒抗体和疫苗在稳健的临床前 针对一系列冠状病毒的模型，包括Select Agents。一个多学科的科学家团队 来自五所具有出色合作记录的机构将进行 建议的研究。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。综合和协同活动 跨项目和核心将推动该计划项目的雄心勃勃的成功完成 研究议程，实现PLUTO的长期目标，即开发防变体的泛 肉瘤病毒和泛β冠状病毒疫苗。这些发现将有助于遏制当前的SARS- COV-2大流行，并降低未来冠状病毒大流行的风险。