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.

总体总结 鉴于历史上曾爆发过冠状病毒，再加上最近出现的 SARS， CoV-2 和 COVID-19 对全球健康和经济造成的不稳定后果， 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 Sarbecoviruses 和 Merbecoviruses。此 P01 程序项目 (PPG) 地址 假设进化设计和优化的 B 细胞和 T 细胞的组合 抗原可以赋予针对 Sarbecoviruses 的广泛和保护性免疫力 目前存在或可能从人畜共患病宿主中出现的梅贝克病毒。 PPG 整合了 11 个领先实验室的工作以及具有专业知识的合作记录 冠状病毒生物学、病毒发病机制、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。所有项目和核心都计划与重点关注的互动研究 设计优化的 B 和 T 细胞抗原以掺入腺病毒 (ChAd) 和 水泡性口炎病毒 (VSV) 载体可用于制造可保护的粘膜和全身疫苗 预防由一系列潜在问题的冠状病毒引起的感染和疾病。 PPG 由执行疫苗接种和感染的中央动物挑战核心提供服务 小鼠和仓鼠实验以及简化数据的中央管理核心 管理和共享，提供向下选择和科学计算分析 决策，促进沟通。我们的提案和抗原设计方案服务于 作为 ChAd 疫苗、基于 VSV 的疫苗或 即使使用此处未直接评估的其他平台（例如 mRNA 疫苗、纳米颗粒等）也是如此。 通过我们的 PPG 的结论，我们设想产生至少一种并且可能多种病毒- 载体疫苗平台可诱导对多种冠状病毒的广谱免疫 包括人类和人畜共患的 Sarbecoviruses 和 Merbecoviruses 可能出现在 未来。

项目成果

Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses.

SARS-CoV-2 NSP12 导向的 CD4 T 细胞反应与针对普通感冒冠状病毒的预引发反应存在广泛交叉反应的证据。

• 发表时间: 2023
• 作者: Westphal, Tim;Mader, Maria;Karsten, Hendrik;Cords, Leon;Knapp, Maximilian;Schulte, Sophia;Hermanussen, Lennart;Peine, Sven;Ditt, Vanessa;Grifoni, Alba;Addo, Marylyn Martina;Huber, Samuel;Sette, Alessandro;Lütgehetmann, Marc;Pischke, Sven;Kw
• 通讯作者: Kw