Wang Chong, Zheng Xuexing, Gai Weiwei, Wong Gary, Wang Hualei, Jin Hongli, Feng Na, Zhao Yongkun, Zhang Weijiao, Li Nan, Zhao Guoxing, Li Junfu, Yan Jinghua, Gao Yuwei, Hu Guixue, Yang Songtao, Xia Xianzhu
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
School of Public Health, Shandong University, Jinan, China.
Antiviral Res. 2017 Apr;140:55-61. doi: 10.1016/j.antiviral.2016.12.019. Epub 2016 Dec 28.
Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.
中东呼吸综合征冠状病毒(MERS-CoV)自2012年出现以来持续传播,死亡率达35.6%,是一种潜在的大流行威胁。迫切需要预防措施和治疗方法来解决这一公共卫生问题。我们在此报告一种由表达MERS-CoV受体结合域(RBD)的嵌合病毒样颗粒(VLP)组成的疫苗的功效。在本研究中,犬细小病毒(CPV)VP2结构蛋白基因与MERS-CoV的RBD融合后可自组装成嵌合球形VLP(sVLP)。sVLP保留了某些细小病毒的特性,如凝集猪红细胞的能力以及与CPV病毒粒子相似的结构形态。用sVLP免疫可在小鼠体内诱导RBD特异性体液免疫和细胞免疫反应。这些动物产生的sVLP特异性抗血清能够阻止假型MERS-CoV进入易感细胞,中和抗体效价达到1:320。通过ELISpot在接种疫苗小鼠的脾细胞中检测到由RBD诱导的分泌IFN-γ、IL-4和IL-2的细胞。此外,接种sVLP或佐剂化sVLP疫苗的小鼠引发了辅助性T细胞1(Th1)和辅助性T细胞2(Th2)介导的免疫反应。我们的研究表明,展示MERS-CoV RBD的sVLP在潜在疫情爆发情况下是有前景的MERS-CoV预防候选物。