Development of a pan-betacoronavirus vaccine

泛β冠状病毒疫苗的研制

• 批准号: 10549480
• 负责人: Florian Krammer
• 金额: $ 61.26万
• 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/10549480
• 关键词: 2019-nCoV; Achievement; Administrative Coordination; Animal Model; Animals; Antibodies; Antibody Response; Antigens; B-Lymphocytes; Binding; COVID-19 pandemic; COVID-19 vaccine; Clinical; Collaborations; Coronavirus; Coronavirus Infections; Coronavirus spike protein; Cross Reactions; Development; Disease; Disease Outbreaks; Environment; Epidemic; Epitopes; Ferrets; Funding; Future; Goals; Human; Humoral Immunities; Immune; Immune response; Immunity; Infection; Institution; Knowledge; Learning; Messenger RNA; Methodology; Middle East Respiratory Syndrome Coronavirus; Modeling; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Pathogenicity; Phenotype; Population; Proteins; Public Health; Readiness; Recombinants; Recording of previous events; Regimen; Research; Research Project Grants; Resources; Role; SARS coronavirus; SARS-CoV-2 B.1.1.529; SARS-CoV-2 B.1.351; SARS-CoV-2 B.1.617.2; SARS-CoV-2 infection; SARS-CoV-2 spike protein; SARS-CoV-2 variant; Sarbecovirus; Scientist; Services; Specificity; Structure; Testing; Time; Update; Vaccination; Vaccine Design; Vaccines; Variant; Viral; Virus; Work; Zoonoses; betacoronavirus; betacoronavirus vaccine; cohort; coronavirus vaccination; cross reactivity; design; efficacy evaluation; efficacy testing; experience; future pandemic; human model; imprint; member; multidisciplinary; neutralizing monoclonal antibodies; novel; pandemic disease; pandemic potential; programs; rational design; receptor binding; response; risk mitigation; seasonal coronavirus; spillover event; synergism; universal coronavirus vaccine; universal influenza vaccine; vaccination strategy; vaccine candidate; vaccine development; vaccine effectiveness; vaccine-induced immunity

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 successful completion of research aims and the long-term goal of the project. 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 a large panel of recombinant monoclonal antibodies against coronavirus spike proteins to aid in defining specificity of immune responses elicited by coronavirus infection and/or vaccination 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- The Research Projects will collaborate with each other with the support of the services provided by Antibody and Animal Model Cores and overall coordination by the Administrative Core. Project 2 will focus on the development and design of variant-proof pan- sarbecovirus vaccines as well as pan-betacoronavirus vaccines 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 integrated and synergistic activities across Projects and Cores will drive successful completion of the program project's ambitious research agenda, enabling achievement of the long-term PLUTO goal of developing viral variant- proof pan-sarbecovirus and pan-betacoronavirus vaccines. These findings will contribute to curbing the current SARS-CoV-2 pandemic and help to 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复杂并生成疫苗的机制 候选人可以引起此类回应。该计划项目标题为“编程长期免疫力 冠状病毒（Pluto）”提案为设计Pan-Sarbecovirus的全面研究计划 和泛 - 甲苯曲霉病毒疫苗，通过在深入的B细胞表征中进行广泛保护 成功疫苗接种和/或感染印象深刻的冠状病毒免疫历史上下文。二 补充研究项目将建立坚固，耐用和受保护的冠状病毒的相关性 体液免疫（项目1）以及病毒变体泛 - 萨尔贝病毒的设计和测试效率和测试效率 PAN-贝曲霉病毒疫苗（项目2）。核心将与两个研究项目协同作用，以支持 成功完成研究目标和项目的长期目标。行政核心将 管理财团，协调跨项目的活动，并创建所需的结构和环境 实现冥王星的目标。抗体核心将开发大量的重组单克隆 针对冠状病毒尖峰蛋白的抗体有助于确定由免疫反应的特异性 人类和动物模型中的冠状病毒感染和/或疫苗接种。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，以评估广泛交叉反应的效率 冠状动脉抗体和疫苗在强大的前 - 研究项目将相互合作 在抗体和动物模型核心提供的服务的支持下，以及通过 行政核心。项目2将重点介绍变体Pan的开发和设计 - SARBECOVIRUS疫苗以及Pan-Betacoronavirus疫苗临床模型均针对一系列 冠状病毒，包括精选剂。来自五个机构的科学家团队的多学科团队 合作的杰出工作记录将进行拟议的研究。集成和 跨项目和核心的协同活动将推动该计划项目的成功完成 雄心勃勃的研究议程，实现了发展病毒变异的长期冥王星目标 证明泛 - 萨尔贝病毒和泛贝曲霉病毒疫苗。这些发现将有助于遏制 当前的SARS-COV-2大流行，有助于减轻冠状病毒未来大流行的风险。