The Development and Evaluation of Pan-Coronavirus Vaccines

泛冠状病毒疫苗的研发与评价

• 批准号: 10420511
• 负责人: Michael S Diamond
• 金额: $ 799.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420511
• 关键词: 2019-nCoV; Address; Adenovirus Vector; Amino Acids; Animal Model; Animals; Antibodies; Antigens; Attenuated; B-Lymphocytes; Biological Assay; Biology; Blood; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 impact; Catalogs; Chiroptera; Cloning; Collaborations; Communication; Computer Analysis; Coronavirus; Coronavirus Infections; Coupled; Data; Decision Making; Development; Diamond; Disease; Disease Outbreaks; Distant; Elements; Evaluation; Feedback; Future; Generations; Genetic Recombination; Goals; Hamsters; Human; Immune; Immune response; Immunity; Immunization; Immunologics; Immunologist; Infection; Intramuscular; Laboratories; Lead; Machine Learning; Merbecovirus; Messenger RNA; Meta-Analysis; Molecular; Mucous Membrane; Mus; Open Reading Frames; Pan Genus; Pre-Clinical Model; Program Research Project Grants; Protein Region; Proteins; Quality Control; RNA vaccine; Readiness; Records; Research Project Grants; Sarbecovirus; Serum; Site; Source; Speed; Structural Biologist; Structure; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Tissues; Vaccination; Vaccine Design; Vaccines; Vesicular stomatitis Indiana virus; Viral Pathogenesis; Viral Vaccines; Viral Vector; Virus; Work; Zoonoses; base; betacoronavirus; coronavirus vaccine; cross immunity; cross reactivity; data management; data sharing; design; efficacy study; experimental study; global health; immunogenicity; innovation; interest; member; nanoparticle; neutralizing antibody; novel coronavirus; novel vaccines; pandemic disease; product development; programs; response; scaffold; structural biology; universal coronavirus vaccine; vaccine candidate; vaccine development; vaccine evaluation; vaccine platform; vector; vector vaccine; virtual

Overall Summary Given the historical outbreaks of coronaviruses, coupled with the recent emergence of SARS- CoV-2 and the destabilizing consequence of COVID-19 on global health and economy, there is an urgent and critical need to develop new vaccines capable of broad protection against existing and future Sarbecoviruses and Merbecoviruses. This P01 program project (PPG) addresses the hypothesis that a combination of evolutionarily-designed and optimized B and T cell antigens can confer broad and protective immunity against Sarbecoviruses and Merbecoviruses that currently exist or could emerge from zoonotic reservoirs. The PPG integrates the work of eleven leading laboratories with records of collaboration that have expertise in coronavirus biology, viral pathogenesis, B and T cell immunity, vaccine development, animal challenge studies, structural biology, antibody structure and function, antigen design, and evolutionary analysis of viruses. All Projects and Cores plan interactive studies with the focused goal of designing optimized B and T cell antigens for incorporation in adenoviral (ChAd) and vesicular stomatitis virus (VSV) vectors to create mucosal and systemic vaccines that protect against infection and disease caused by a range of coronaviruses of potential concern. The PPG is served by a central Animal Challenge Core that performs vaccination and infection experiments in mice and hamsters and a central Administrative Core that streamlines data management and sharing, provides computational analysis for down-selection and scientific decision-making, and facilitates communication. Our proposal and antigen design program serves as a blueprint for possible product development with ChAd vaccines, VSV-based vaccines, or even with other platforms (e.g., mRNA vaccines, nanoparticles, etc.) not directly evaluated here. By the conclusion of our PPG, we envision generating at least one and likely multiple viral- vectored vaccine platforms that induce broad spectrum immunity to multiple coronaviruses of concern including human and zoonotic Sarbecoviruses and Merbecoviruses that could emerge in the future.

总体汇总 鉴于冠状病毒的历史爆发，加上最近出现的SARS- COV-2和COVID-19对全球健康和经济的不稳定影响， 迫切需要开发能够广泛保护现有疫苗的新疫苗， 以及未来的Sarbecovirus和Merbecovirus。本P01程序项目（PPG） 假设进化设计和优化B和T细胞的组合 抗原可以赋予针对肉瘤病毒的广泛的保护性免疫， 目前存在或可能从人畜共患病宿主中出现的鼠伤寒病毒。的PPG 将11个领先实验室的工作与具有专业知识的合作记录相结合 在冠状病毒生物学、病毒发病机理、B和T细胞免疫、疫苗开发、动物 挑战研究，结构生物学，抗体结构和功能，抗原设计，以及 病毒的进化分析所有项目和核心计划互动研究与重点 目的是设计用于掺入腺病毒（ChAd）的优化的B和T细胞抗原， 水泡性口炎病毒（VSV）载体，以创建粘膜和全身疫苗， 预防由一系列潜在的冠状病毒引起的感染和疾病。的PPG 由一个中央动物挑战中心提供服务， 小鼠和仓鼠的实验，以及简化数据的中央管理核心 管理和共享，为向下选择提供计算分析， 决策，促进沟通。我们的建议和抗原设计程序服务于 作为ChAd疫苗、基于VSV的疫苗或 即使对于其它平台（例如，mRNA疫苗、纳米颗粒等）这里不直接评价。 通过我们的PPG的结论，我们设想产生至少一个和可能的多个病毒- 诱导对多种冠状病毒的广谱免疫的载体疫苗平台， 包括人类和人畜共患的Sarbecoviruses和Merbecoviruses可能出现在 未来