Development of a pan-betacoronavirus vaccine

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 了解控制广泛保护性免疫反应和产生疫苗的机制 候选人能够得到这样的回答。题为“规划持久免疫”的方案项目 冠状病毒（PLUTO）”提出了一个全面的研究计划， 和泛β-冠状病毒疫苗，通过在免疫系统中应用深入的B细胞表征， 冠状病毒免疫史的背景是连续接种疫苗和/或感染。两 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）以及抗病毒变异泛肉瘤病毒的设计和测试功效， 泛β冠状病毒疫苗（项目2）。核心研究中心将与两个研究项目协同作用， 顺利完成研究目标和项目的长期目标。行政核心将 管理联合体，协调跨项目活动，并创建所需的结构和环境 完成冥王星的目标抗体核心将开发一个重组单克隆抗体的大面板。 针对冠状病毒刺突蛋白的抗体，以帮助确定由以下引起的免疫应答的特异性： 冠状病毒感染和/或疫苗接种。动物模型核心将提供一个 拥有批准、设施和专业知识的中央资源，以评估广泛交叉反应的有效性 冠状病毒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， 行政核心。项目2将重点开发和设计防变异泛- 肉瘤病毒疫苗以及泛β冠状病毒疫苗的临床模型， 冠状病毒，包括选择代理。一个由来自五个机构的科学家组成的多学科团队， 将进行拟议的研究。的统筹 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PLUTO开发病毒变体的长期目标- 证明泛肉瘤病毒和泛β冠状病毒疫苗。这些发现将有助于遏制 目前的SARS-CoV-2大流行，并有助于减轻未来冠状病毒大流行的风险。

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.