Optimization of G Protein-based RSV Vaccines

摘要 这项建议的总体目标是开发基于G蛋白的呼吸道合胞病毒 (RSV)疫苗。呼吸道合胞病毒是婴幼儿下呼吸道疾病最常见的原因。 世界各地的儿童。它在老年人的呼吸道疾病中也发挥着重要作用 免疫功能受损的病人。发展RSV既有迫切需要，也有令人信服的理由 疫苗。过去和现在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，但 有效的RSV疫苗仍然难以捉摸。RSV G蛋白负责病毒对宿主的附着 细胞。然而，到目前为止，只有一种基于G的疫苗在人类身上进行了研究。担心…… RSV毒株间的高度变异性及其表面结构和体外有限的知识 功能导致其作为候选疫苗的使用有限。的最新进展 了解G在病毒感染和疾病中的作用表明应该认识到G 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，基础疫苗可以提供对RSV感染的保护。此外， 我们已经应用了合理的设计方法来生成具有很高潜力的候选人 提供广泛的保护。这项SBIR提案的主要目标是严格评估 两个动物模型的候选人。拟议的工作将为下一步行动提供关键的基础 基于G蛋白的RSV候选疫苗走向临床研究。

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.