Structural Biology of Influenza Epitopes

流感表位的结构生物学

基本信息

批准号：
10272199
负责人：
Audray Harris
金额：
$ 85.86万
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/10272199
关键词：
3-Dimensional Address Affect Animals Antibodies Antigens Architecture Area Attenuated B-Lymphocytes Binding Biochemical Bite Coin Communicable Diseases Competence Complex Development Electron Microscopy Epitopes Evaluation Formulation Future Geometry Glycoproteins Goals Health Hemagglutinin Human Immune response Immune system Immunity Immunologics Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H7N9 Subtype Influenza A virus Influenza B Virus Investigation Membrane Glycoproteins Mission Molecular Nature Pharmaceutical Preparations Phase Population Proteins Public Health Recombinants Research Scaffolding Protein Seasons Structure Subunit Vaccines T-Lymphocyte T-Lymphocyte Epitopes Testing United States National Institutes of Health Vaccine Design Vaccines Viral Viral Vaccines Virion Virus Virus-like particle Zoonoses adaptive immune response animal efficacy arm base design efficacy study immunogenicity influenza outbreak influenza virus vaccine influenzavirus innovation molecular modeling nanoparticle nanotechnology platform neutralizing antibody pandemic disease scaffold structural biology three dimensional structure transmission process universal influenza vaccine vaccine development

项目摘要

Influenza viruses remains a major health burden due to their abilities to change the epitopes of their major surface glycoprotein hemagglutinin. Although conserved influenza epitopes have been identified, there is a fundamental gap in understanding and correlating the disposition of conserved influenza 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 influenza epitopes cannot be understood in molecular details. In FY 2020, we characterized the glycoprotein and virion organizations of influenza viruses with internal core structures and the disposition of viral glycoprotein antigens within commercial influenza subunit vaccines with antigens for type A and B influenza viruses. Also, we have continued both designing and characterizing various nanoparticles displaying conserved epitopes from influenza antigens, such as hemagglutinin. In addition, we have established significant milestones in the design, purification, 3D structural analysis, and animal efficacy studies of nanoplatforms that have conserved epitopes from both group 1 and group 2 influenza A viruses. These results are significant and relevant to public health because it is expected to expand understanding of the structure and epitope disposition of influenza epitopes on nanoplatforms and HA. This will aid immunogen evaluation and design for more efficacious season vaccines and facilitate the development of universal influenza vaccines.

由于其能力改变其主要表面糖蛋白血凝集素的表现能力，因此流感病毒仍然是重大的健康负担。尽管已经鉴定出保守的流感表位，但在理解和将保守的流感表位对亚基疫苗的处置和设计具有免疫原性的纳米颗粒的处置存在基本差距。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守的流感表位，就无法通过分子细节来理解。在2020财年，我们表征了具有内部核心结构的流感病毒的糖蛋白和病毒蛋白组织，并在商业流感亚基疫苗中与A型和B型流感病毒的抗原中的病毒糖蛋白抗原处置。此外，我们继续设计和表征各种纳米颗粒，这些纳米颗粒显示出来自流感抗原（例如黑凝集素）的保守表位。此外，我们在设计，纯化，3D结构分析和动物功效研究方面建立了重要的里程碑，这些纳米植物具有保守1组和第2组流感病毒的表位的纳米植物。这些结果很重要，并且与公共卫生有关，因为它有望扩大对纳米植物和HA的流感表位的结构和表位处置的理解。这将有助于免疫原子评估和设计，以实现更有效的季节性疫苗，并促进通用流感疫苗的开发。