Development of a pan-betacoronavirus vaccine

SARS-CoV-2大流行是一场特殊的公共卫生危机，突显了需要更好地 理解广泛保护性免疫反应的控制机制和疫苗的产生 能够引起这样的反应的候选人。题为《规划长效免疫》的项目 对冠状病毒(冥王星)提出了设计泛肉瘤病毒的全面研究计划 和泛β冠状病毒疫苗，通过应用深入的B细胞特征在 连续接种疫苗和/或感染所留下的冠状病毒免疫史的背景。二 补充性研究项目将建立强健、持久和保护性冠状病毒的相关性 体液免疫(项目1)以及病毒防变异泛肉瘤病毒和 泛贝塔冠状病毒疫苗(项目2)。这些核心将与两个研究项目协同工作，以支持 圆满完成研究目标和项目的长期目标。行政核心意志 管理联合体，协调跨项目活动，并创造所需的结构和环境 来完成冥王星的目标。抗体核心将开发一大批重组单抗 抗冠状病毒刺突蛋白抗体有助于确定由冠状病毒刺突蛋白引起的免疫反应的特异性 冠状病毒在人类和动物模型中的感染和/或接种。动物模型核心将提供一个 具有审批、设施和专业知识的中央资源，用于评估广泛交叉反应的效果 冠状病毒抗体和疫苗在强健的前期研究项目中将相互合作 在抗体和动物模型核心提供的服务的支持下，以及由 管理核心。项目2将重点开发和设计防变底盘。 针对多种疾病的肉瘤病毒疫苗和泛贝塔冠状病毒疫苗的临床模型 冠状病毒，包括精选试剂。一个由来自五个机构的多学科科学家组成的团队 优秀的合作记录将进行拟议的研究。集成的和 跨项目和核心的协同活动将推动计划项目的成功完成 雄心勃勃的研究议程，使开发病毒变体的冥王星长期目标得以实现- 验证泛肉瘤病毒和泛贝塔冠状病毒疫苗。这些发现将有助于遏制 目前的SARS-CoV-2大流行有助于降低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.