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的机制并产生 候选疫苗能够引起这种反应，该计划项目名为“持久编程”。 对冠状病毒的免疫（PLUTO）”提出了一项全面的研究计划，旨在设计泛 通过深入应用 B 细胞，提供广泛保护的 sarbecovirus 和 pan-betacoronavirus 疫苗 连续疫苗接种所印记的冠状病毒免疫史背景下的表征 和/或感染。两个互补的研究项目将建立稳健、持久的关联。 和保护性冠状病毒体液免疫（项目1）以及病毒的设计和功效测试 防变异泛 sarbecovirus 和泛 betacoronavirus 疫苗（项目 2）将具有协同作用。 这两个研究项目支持顺利完成研究目标。 核心将管理联盟，协调跨项目活动，并创建结构和 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) 以确定特异性和 人类和动物中冠状病毒感染和/或疫苗接种引起的免疫反应 动物模型核心将提供具有批准、设施和专业知识的中央资源。 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的功效 针对一系列冠状病毒的模型，包括选择代理由多学科科学家组成的团队。 来自具有出色合作记录的五个机构将主持 拟议的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。 跨项目和核心的合作将推动该计划雄心勃勃的目标的成功完成 研究议程，从而实现 PLUTO 开发防变异泛型的长期目标 这些发现将有助于遏制当前的 SARS 病毒。 CoV-2 大流行并降低未来冠状病毒大流行的风险。