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.

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