我国大陆流行的人呼吸道合胞病毒F蛋白抗原位点动态变异研究

Human respiratory syncytial virus (HRSV) is a leading Viral pathogen of acute lower respiratory tract infections and hospitalizations in children less than 5 years, and circulated widely in China. At present, there is no effective vaccine used to protect the people from HRSV infection, and Palivizumab, the only monoclonal antibody approved and used by developed countries for protecting premature and vulnerable children was not used in China. The F protein is reported to be highly conserved between the two subgroups worldwide. However, there was no systematic study of the nucleotide, amino acid and the antigenic variation of HRSV F protein with years and regions conducted in China, which limits the development of our vaccine and antibody with independent intellectual property rights and clinical application. Hence, it is meaningful and necessary to study on the molecular evolution and antigenic variation of China HRSV with different years and regions systematically and clarified the important antigenic dynamic changes of HRSV F protein. Screening the monoclonal antibodies against domestic HRSV strains and the sensibility of China HRSV strain to Palivizumab will also be performed. These studies could provide the scientific data for the molecular epidemiology of China HRSV and have the important implications for basic science of the development of vaccine and antibody with independent intellectual property rights in mainland China.

人呼吸道合胞病毒（Human respiratory syncytial virus, HRSV）是引起5岁以下婴幼儿急性下呼吸道感染的主要病原体之一，并在我国广泛流行，尚无有效的疫苗来预防HRSV引起的感染，发达国家已上市针对HRSV F蛋白的帕丽珠单克隆抗体用于早产儿和体弱婴幼儿的被动保护，然而我国尚未引进。国际报道欧美流行的HRSV F蛋白编码基因高度保守，但我国尚未系统开展不同年代和地域流行的HRSV F蛋白的核苷酸、氨基酸和抗原位点的变异变迁分析，因而制约着我国自主知识产权HRSV疫苗及单抗的开发和临床申报。因此系统开展我国不同地域和年份流行HRSV的分子进化特征和抗原变异变迁规律，深入阐明我国流行HRSV F蛋白抗原中和位点动态变异，筛选可中和我国本土流行株重要抗原位点的单抗，评价我国本土株在帕丽珠单抗作用靶点的变异，对我国自主预防性单抗的开发和疫苗研制具有重要的基础科学意义。

人呼吸道合胞病毒（Human respiratory syncytial virus, HRSV）是引起5岁以下婴幼儿急性下呼吸道感染的主要病原体之一，并在我国广泛流行。目前，尚无有效的疫苗来预防HRSV引起的感染，发达国家已上市针对HRSV F蛋白的帕丽珠单克隆抗体用于早产儿和体弱婴幼儿的被动保护，然而我国尚未引进。国际报道欧美流行的HRSV F蛋白编码基因高度保守，但我国尚未系统开展不同年代和地域流行的HRSV F蛋白的核苷酸、氨基酸和抗原位点的变异变迁分析，因而制约着我国自主知识产权HRSV疫苗及单抗的开发和临床申报。因此我们在本项研究中，系统开展了我国不同地域和年份流行的HRSV分子进化特征和抗原变异变迁规律，结果显示我国近10年来HRSV流行呈现各亚型和各基因型别交替流行和共流行的特征；而ON1和BA9基因型已经成为我国近年来HRSV流行的优势基因型。随后我们又选取代表株对F蛋白编码基因全长序列进行测序，获得了HRSV F基因的核苷酸和氨基酸序列信息，深入阐明了我国流行HRSV F蛋白抗原中和位点的多态性，鉴定了重要抗原位点的变异。中和实验结果显示中国流行HRSV代表株对帕利珠单克隆抗体敏感，说明针对抗原位点II区的帕利珠单克隆抗体对中国流行株具有中和作用。本研究也评价了我国本土株在帕丽珠单抗作用靶点的变异，对我国自主预防性单抗的开发和疫苗研制具有重要的基础科学意义。