Development of Broad Coronavirus Immunity Targeting the Fusion Peptide

针对融合肽的广泛冠状病毒免疫的开发

• 批准号: 10424573
• 负责人: Daniel Kulp
• 金额: $ 22.88万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-09 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424573
• 关键词: 2019-nCoV; Advanced Development; Algorithm Design; Animals; Antibodies; Antigens; Award; B-Lymphocytes; Binding; Biophysics; COVID-19; COVID-19 pandemic; COVID-19 patient; Cellular Immunity; China; Cities; Clinical; Communicable Diseases; Coronavirus; Coronavirus spike protein; DNA delivery; Denmark; Development; Devices; Disease; Disease Outbreaks; Electroporation; Emergency Situation; Epitopes; Evaluation; Frequencies; Generations; Genetic; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunization; Immunization Programs; Investigation; Length; Link; Middle East Respiratory Syndrome; Middle East Respiratory Syndrome Coronavirus; Mink; Mutate; Mutation; Parents; Peptides; Pharmaceutical Preparations; Plasmids; Polymerase; Polysaccharides; Population; Proteins; Publishing; Reagent; Recovery; SARS coronavirus; SARS-CoV-2 spike protein; Site; Structure; Technology; Therapeutic; Time; Translations; United States National Institutes of Health; Vaccine Clinical Trial; Vaccines; Virus; Widespread Disease; Zoonoses; animal data; base; combat; convalescent plasma; coronavirus vaccine; cross reactivity; design; experimental study; human coronavirus; immunogenic; improved; inhibitor; interest; medical countermeasure; nanoparticle; neutralizing antibody; novel coronavirus; nucleic acid delivery; plasmid DNA; pre-clinical; remdesivir; response; small molecule; transmission process; vaccine effectiveness

Project Summary This revised application was originally responding to the Emergency Award ‘Rapid Investigation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19)’ submitted through PAR-20-177. However, we are submitting the revised application, upon advice from NIH, to the parent PA-20-195 with a due date of Nov 16th 2020. The application is titled ‘Development of Broad Coronavirus Immunity Targeting the Fusion Peptide’. The assembled team brings together highly complementary expertise in order to develop a unique coronavirus vaccine approach to provide more effective, focused and broadened humoral immunity. This proposal focuses on the fusion peptide site of vulnerability as it has been understudied, it is highly conserved and recently been identified as an epitope of neutralizing antibodies in human convalescent sera. The project aims are: (1) Develop pan- coronavirus fusion peptide nanoparticle and trimer immunogens (2) Develop immunization regimes to induce broadly neutralizing antibodies using nucleic acid delivery.

项目概要 此修订后的申请最初是响应紧急奖“快速调查严重事件” 急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 和 2019 年冠状病毒病 (COVID-19)’ 通过 PAR-20-177 提交。然而，根据 NIH 的建议，我们正在将修订后的申请提交给 母版 PA-20-195，截止日期为 2020 年 11 月 16 日。该申请的标题为“Development of Broad” 针对融合肽的冠状病毒免疫”。集结的团队汇聚了高度 互补的专业知识，以开发独特的冠状病毒疫苗方法，提供更有效、 集中并扩大体液免疫。该提案的重点是融合肽位点 脆弱性，因为它已被充分研究，它是高度保守的，最近被确定为 人类恢复期血清中中和抗体的表位。项目目标是： (1) 发展泛 冠状病毒融合肽纳米颗粒和三聚体免疫原（2）开发免疫方案以诱导 使用核酸递送广泛中和抗体。