Zhou Hui, Huang Yang, Yuan Songhua, Li Yuanyuan, Wu Shuyan, Xu Jianqing, Huang Rui
Medical College of Soochow University, Suzhou, Jiangsu 215125, PR China; ENT Department of the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
VacDiagn Biotechnology, Suzhou, Jiangsu 215125, PR China.
Vaccine. 2017 Jan 5;35(2):305-312. doi: 10.1016/j.vaccine.2016.11.051. Epub 2016 Nov 30.
Seasonal and emerging epidemics caused by influenza virus remain as a public health concern and an economic burden. The weak immunogenicity of conserved epitopes on hemagglutinin that induces broad protective immune responses is the main obstacle to the development of universal vaccines. In the present report, we designed the cross-subtypic sequential vaccination strategy and evaluated its neutralizing antibody (nAb) activity by pseudovirus-based neutralization assays. The results clearly indicated that compared with traditional vaccines strategy, the cross-subtypic sequential immunization could significantly induce a broad serum cross-reactive nAb response in mice as well as against homologous strains, and provide protection from heterologous virus PR8 (H1N1) challenge. Furthermore, we isolated two monoclonal antibodies from sequentially immunized mice, which had potent broadly neutralizing activity against multiple influenza strains. These data suggest the feasibility of sequential immunization in universal flu vaccine development.
由流感病毒引起的季节性和新出现的流行病仍然是一个公共卫生问题和经济负担。血凝素上保守表位的弱免疫原性诱导广泛的保护性免疫反应，这是通用疫苗开发的主要障碍。在本报告中，我们设计了跨亚型序贯疫苗接种策略，并通过基于假病毒的中和试验评估其中和抗体（nAb）活性。结果清楚地表明，与传统疫苗策略相比，跨亚型序贯免疫可显著诱导小鼠产生广泛的血清交叉反应性nAb反应以及针对同源毒株的反应，并提供针对异源病毒PR8（H1N1）攻击的保护。此外，我们从序贯免疫的小鼠中分离出两种单克隆抗体，它们对多种流感毒株具有强大的广泛中和活性。这些数据表明序贯免疫在通用流感疫苗开发中的可行性。
