Structural Biology of Influenza Epitopes

流感表位的结构生物学

基本信息

批准号：
9786482
负责人：
Audray Harris
金额：
$ 158.13万
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/9786482
关键词：
Address Affect Animals Antibodies Antigens Architecture Area Attenuated B-Lymphocytes Binding Biochemical Bite Coin Communicable Diseases Competence Complex Cryoelectron Microscopy Development Epitopes Evaluation Formulation Future Geometry Goals Health Hemagglutinin Human Immune response Immune system Immunity Immunologics Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H7N9 Subtype Investigation Membrane Glycoproteins Mission Molecular Nature Pharmaceutical Preparations Phase Population Proteins Public Health Recombinants Research Scaffolding Protein Structure Subunit Vaccines T-Lymphocyte T-Lymphocyte Epitopes Testing United States National Institutes of Health Vaccine Design Vaccines Viral Vaccines 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 nano nanoparticle neutralizing antibody pandemic disease particle scaffold stem structural biology transmission process universal influenza vaccine vaccine development

项目摘要

The influenza virus remains a major health burden due to its abilities to change the epitopes of the major surface glycoprotein hemagglutinin, and its zoonotic nature, allowing transmission of animal viruses to humans to which the human population has no preexisting immunity. 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 2018, 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 viruses. Furthermore, we have structurally characterized symmetrical nanoparticles and non-symmetrical particles, such as influenza virus-like particles (VLPs), as platforms to carry and display influenza antigens. These results are significant and relevant to public health because they are expected to expand understanding of the structure and epitope disposition of influenza epitopes on nanoplatforms. This will aid immunogen evaluation and design for more efficacious seasonal vaccines and facilitate the development of universal influenza vaccines.

流感病毒仍然是重大的健康负担，因为它可以改变主要表面糖蛋白血凝集素的表位及其人畜共患性质，从而使动物病毒传播到人类没有先前存在的免疫力。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2018财年，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（例如血凝素）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。此外，我们在结构上表征了对称的纳米颗粒和非对称的颗粒，例如流感病毒样颗粒（VLP），是携带和显示流感抗原的平台。这些结果与公共卫生相关，因为它们有望扩大对纳米植物表现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。