Development of a pan-betacoronavirus vaccine

泛β冠状病毒疫苗的研制

基本信息

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
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/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

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 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。成功完成研究目标和项目的长期目标。管理联盟，协调跨项目活动，并创建所需的结构和环境为了实现 PLUTO 的目标，Antibody Core 将开发大量重组单克隆抗体。针对冠状病毒刺突蛋白的抗体有助于确定由冠状病毒引起的免疫反应的特异性动物模型核心将提供人类和动物模型中的冠状病毒感染和/或疫苗接种。具有批准、设施和专业知识的中央资源，用于评估广泛交叉反应的功效冠状病毒抗体和疫苗处于强有力的前期研究项目将相互合作在抗体和动物模型核心提供的服务支持和总体协调下管理核心项目 2 将重点关注防变异泛型的开发和设计。 sarbecovirus 疫苗以及泛 betacoronavirus 疫苗临床模型针对一系列冠状病毒，包括来自五个机构的多学科科学家团队，他们拥有出色的合作记录将进行拟议的研究。跨项目和核心的协同活动将推动该计划的成功完成雄心勃勃的研究议程，能够实现 PLUTO 开发病毒变种的长期目标 - 这些发现将有助于遏制泛冠状病毒和泛β冠状病毒疫苗。当前的 SARS-CoV-2 大流行并有助于降低未来冠状病毒大流行的风险。