Wang Xiaohua, Xu Wei, Tong Deyan, Ni Jing, Gao Haifeng, Wang Ying, Chu Yiwei, Li Pingping, Yang Xiaoming, Xiong Sidong
Institute for ImmunoBiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, PR China.
Immunol Lett. 2008 Aug 15;119(1-2):71-7. doi: 10.1016/j.imlet.2008.04.005. Epub 2008 May 19.
Epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) are being developed as a means for increasing vaccine potency. In this study, we identified four B cell epitopes from the spike (S) and membrane (M) protein through bioinformatics analysis and constructed a multi-epitope DNA vaccine. Intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory humoral immune response to at least two candidate epitopes, S(437-459) and M(1-20). A DNA prime-protein boost strategy greatly enhanced the antibody generation and the immune sera not only reacted with the lysates of SARS-CoV-infected Vero cells but also neutralized the cytopathic effect of SARS by 75% at 1:160 dilution. The novel immunogenic S protein peptide revealed in this study provides new target for SARS vaccine design; and our work indicated multi-epitope DNA vaccine as an effective means for eliciting polyvalent humoral immune response against SARS-CoV.
旨在诱导针对严重急性呼吸综合征相关冠状病毒(SARS-CoV)的特异性抗体反应的基于表位的疫苗正在作为提高疫苗效力的一种手段进行研发。在本研究中,我们通过生物信息学分析从刺突(S)蛋白和膜(M)蛋白中鉴定出四个B细胞表位,并构建了一种多表位DNA疫苗。用该疫苗对小鼠进行肌肉注射免疫足以诱导针对至少两个候选表位S(437 - 459)和M(1 - 20)的特异性初免以及长期记忆体液免疫反应。DNA初免-蛋白加强策略极大地增强了抗体产生,免疫血清不仅与SARS-CoV感染的Vero细胞裂解物反应,而且在1:160稀释度下能中和75%的SARS细胞病变效应。本研究中揭示的新型免疫原性S蛋白肽为SARS疫苗设计提供了新靶点;我们的工作表明多表位DNA疫苗是引发针对SARS-CoV的多价体液免疫反应的有效手段。