Optimization of G Protein-based RSV Vaccines

基于 G 蛋白的 RSV 疫苗的优化

• 批准号: 10079203
• 负责人: SHENGQIANG LI
• 金额: $ 29.95万
• 依托单位: SCIOGEN, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10079203
• 关键词: Adjuvant; Animal Model; Animals; Antibodies; Attenuated Live Virus Vaccine; Betaretrovirus; Binding; Biological Assay; Blocking Antibodies; Cells; Child; Clinical Research; Collaborations; Combined Vaccines; Cotton Rats; Cytoplasmic Tail; Development; Disease; Elderly; Emulsions; Engineering; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Escherichia coli; Evaluation; Exhibits; Failure; Foundations; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Goals; Gold; Grant; Human; Immune Sera; Immune System Diseases; Immune response; Immunization; Immunize; Immunocompromised Host; In Vitro; Infant; Innate Immune Response; Knowledge; Licensing; Lower respiratory tract structure; Lung; Lung diseases; Membrane Glycoproteins; Modeling; Mucins; Mus; Oils; Pathology; Phase; Play; Production; Proteins; Recombinant Delta Chemokine; Recombinant Vaccines; Recombinants; Research Design; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory syncytial virus; Role; Small Business Innovation Research Grant; Structure; Surface; System; Technology; Universities; Vaccines; Viral; Viral Load result; Virulent; Virus; Virus Diseases; Water; Work; airway epithelium; attachment protein G; base; design; in vivo; mouse model; receptor; respiratory; vaccine candidate; vaccine development; vaccine efficacy; vaccine safety

Abstract The overall objective of this proposal is to develop G protein-based respiratory syncytial virus (RSV) vaccine. RSV is the most common cause of lower respiratory illness in infants and young children worldwide. It also plays significant role in respiratory illness in the elderly and in immunocompromised patients. There is an urgent need and compelling reasons to develop RSV vaccine. Past and current development efforts are mainly focused on F protein-based recombinant vaccines and live attenuated vaccines. Despite major efforts for several decades, an effective RSV vaccine remains elusive. RSV G protein is responsible for viral attachment to host cells. However, only a single G-based vaccine has been studied in humans to date. Concern over the high variability across RSV strains and limited knowledge in its surface structure and in vitro function have contributed to its limited use as vaccine candidate. Recent advances in understanding the roles of G in viral infection and in disease indicate that G should be recognized as an important target for vaccine development. Preliminary studies indicate that our G protein- based vaccine can provide protection against RSV infection in the animal models. Furthermore, we have applied a rational design approach to generate candidates that have high potential to induce broad protection. The main objective of this SBIR proposal is to rigorously evaluate the candidates in two animal models. The proposed work will provide a critical foundation to move the G protein-based RSV vaccine candidate toward clinical study.

摘要 本提案的总体目标是开发基于G蛋白的呼吸道合胞病毒 (RSV)疫苗RSV是婴幼儿下呼吸道疾病的最常见原因 世界各地的儿童。它还在老年人呼吸系统疾病中发挥重要作用， 免疫功能低下的患者。有迫切的需要和令人信服的理由来开发RSV 疫苗过去和当前的开发工作主要集中在基于F蛋白的 重组疫苗和减毒活疫苗。尽管几十年来做出了重大努力， 有效的RSV疫苗仍然难以捉摸。RSV G蛋白负责病毒附着到宿主 细胞然而，迄今为止，只有一种基于G的疫苗在人类中进行了研究。关切 RSV毒株之间的高度变异性及其表面结构和体外研究的知识有限 功能导致其作为候选疫苗的有限使用。的最新进展 了解G在病毒感染和疾病中的作用表明G应该被认识到， 作为疫苗开发的重要目标。初步研究表明我们的G蛋白- 在动物模型中，基于RSV的疫苗可以提供针对RSV感染的保护。此外，委员会认为， 我们采用了合理的设计方法来产生具有高潜力的候选人， 导致广泛保护。该SBIR提案的主要目标是严格评估 两种动物模型中的候选人。拟议的工作将提供一个关键的基础， 以G蛋白为基础RSV疫苗候选物进入临床研究。