Structural Biology and Biochemistry of Coronavirus

冠状病毒的结构生物学和生物化学

基本信息

批准号：
10927948
负责人：
Audray Harris
金额：
$ 0.58万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10927948
关键词：
2019-nCoV 3-Dimensional Address Affect Animals Antibodies Antigenic Variation Antigens Architecture B-Lymphocytes Binding Biochemical COVID-19 pandemic Chimeric Proteins Coin Communicable Diseases Competence Complex Coronavirus Coronavirus spike protein Development Disease Electron Microscopy Encapsulated Epitopes Formulation Genome Geometry Glycoproteins Goals Health Human Immune response Immune system Immunologics Innate Immune Response Membrane Membrane Proteins Middle East Respiratory Syndrome Mission Molecular Nucleocapsid Proteins Phase Population Proteins Public Health Recombinants Research SARS coronavirus Scaffolding Protein Seasons Structural Biochemistry Structure Subunit Vaccines T-Lymphocyte T-Lymphocyte Epitopes Testing United States National Institutes of Health Vaccine Production Vaccines Variant Viral Viral Structural Proteins Viral Vaccines Virion Virus Work Zoonoses adaptive immune response animal coronavirus arm design immunogenicity innovation molecular modeling nanoparticle nanotechnology platform neutralizing antibody pandemic potential pandemic virus particle scaffold structural biology structural glycoprotein universal coronavirus vaccine vaccine efficacy vaccine formulation vaccine platform vaccine-induced antibodies viral RNA

项目摘要

Coronaviruses remain both a seasonal health burden and pandemic threat due to the antigenic variation of viral glycoproteins and the ability of animal coronaviruses to cause zoonotic infections in humans. Although conserved epitopes have been identified, there is a fundamental gap in understanding and correlating the disposition of conserved coronavirus epitopes on subunit vaccines and designed nanoparticles with immunogenicity. Lack of such information represents important problems and until they are addressed optimal display of conserved coronavirus epitopes cannot be understood in molecular details. In FY 2023, we established milestones for the expression and purification of structure-based immunogens in order to produce chimeric proteins that carry antigenically conserved epitopes from coronaviruses. These designed chimeric protein antigens will assist in understanding how to optimize the display and immunogenicity of conserved coronavirus epitopes on vaccine platforms. This work is significant and relevant to public health because information on how to increase the elicited protective immune responses to conserved coronavirus epitopes will aid in the development of more efficacious vaccines to different antigenic variants of coronaviruses. This is important because coronaviruses can be both seasonal and pandemic viruses in the human population.

由于病毒糖蛋白的抗原变异，冠状病毒既是季节性健康负担和大流行威胁，又是动物冠状病毒引起人畜共患感染的能力。尽管已经鉴定出保守的表位，但在理解和将保守的冠状病毒表位的处置与亚基疫苗和设计具有免疫原性的纳米颗粒的处置相关联存在基本差距。缺乏这样的信息代表了重要的问题，直到解决这些问题的最佳表现为保留的冠状病毒表位，就无法通过分子细节来理解。在2023财年，我们建立了基于结构的免疫原的表达和纯化的里程碑，以产生嵌合蛋白，这些嵌合蛋白具有抗原保守的冠状病毒。这些设计的嵌合蛋白抗原将有助于了解如何优化疫苗平台上保守的冠状病毒表位的显示和免疫原性。这项工作与公共卫生很重要，因为有关如何增加对保守的冠状病毒表位的保护性免疫反应的信息将有助于开发更有效的疫苗，以促进冠状病毒的不同抗原型变异。这很重要，因为冠状病毒可能是人口中的季节性和大流行病毒。