孕后期DS/cav1疫苗接种预防子代RSV感染的有效性及基于安全策略的疫苗优化机制研究

Respiratory Syncytial Virus (RSV) is the most common pathogen of lower respiratory infection in children below 5 years of age, so far there is no licenced vaccine for prophylaxis. Recent breakthroughs in determining the structure of fusion (F) glycoprotein have yielded the most promising vaccine DS/cav1. However there is no data from infants immunized with DS/cav1. If the strategy for protecting infants through immunize pregnant women to boost pre-existing memory B cells leading to an increased transfer of maternal antibody can provide infant protection through the first months of life need to be investigated. Meanwhile there is also a safety concern that should have to be addressed for DS/cav1 maternal immunization. In this research we sought to investigate the influence factors of protection and the antibody dependent enhancement (ADE) of maternal antibody transferred by pregnant woman immunized with DS/cav1. At the same time we proposed an innovative strategy based on our previous data in order to improve the the efficacy of DS/cav1 vaccine and lower the risk of ADE through construct the 201 mutation within Antigenic site ø and epitope Ⅰ-Ⅴ gene knock-off. The comments of this research will delivery new approaches on DS/cav1 development and the immunization strategy for the future clinical trials of RSV as well as other viruses.

作为引起5岁以下婴幼儿下呼吸道感染最常见的病毒病原,呼吸道合胞病毒(RSV)迄今仍缺乏主动免疫疫苗。近年来RSV疫苗研究取得重大突破，Pre F蛋白疫苗DS/cav1成为最具潜力的RSV疫苗，DS/cav1免疫孕后期孕妇，可否使小婴儿被动获得高浓度高效能RSV中和抗体，在生命早期发挥抗病毒效应及是否存在诱发抗体依赖性增强效应（ADE）的风险亟待研究。在前期工作基础上，本课题首先对DS/cav1孕后期接种对生命早期保护力及影响因素进行研究，其次对母源性RSV抗体诱发ADE风险因素及机制进行探索，创新性提出Antigenic site ø 201表位突变及Ⅰ-Ⅴ表位封闭等基于安全因素的疫苗优化策略，具有很好的原创性和应用前景。研究结果必将为RSV PreF疫苗接种人群、接种方案、及基于有效性和安全性的疫苗优化策略等关键环节提供重要理论依据，同时也可为其他疫苗母孕期接种评估及改进提供重要参考。