Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice

被引:78
作者
Wang, Chong [1 ,2 ]
Zheng, Xuexing [3 ]
Gai, Weiwei [1 ,4 ]
Wong, Gary [5 ]
Wang, Hualei [1 ,6 ]
Jin, Hongli [1 ]
Feng, Na [1 ,6 ]
Zhao, Yongkun [1 ,6 ]
Zhang, Weijiao [1 ,4 ]
Li, Nan [1 ]
Zhao, Guoxing [1 ]
Li, Junfu
Yan, Jinghua [5 ]
Gao, Yuwei [1 ,6 ]
Hu, Guixue [7 ]
Yang, Songtao [1 ,6 ]
Xia, Xianzhu [1 ,6 ]
机构
[1] Acad Mil Med Sci, Key Lab Jilin Prov Zoonosis Prevent & Control, Inst Mil Vet, Changchun, Peoples R China
[2] Chinese Acad Agr Sci, State Key Lab Vet Biotechnol, Harbin Vet Res Inst, Harbin, Peoples R China
[3] Shandong Univ, Sch Publ Hlth, Jinan, Peoples R China
[4] Jilin Univ, Coll Vet Med, Changchun, Peoples R China
[5] Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing, Peoples R China
[6] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Jiangsu, Peoples R China
[7] Jilin Agr Univ, Coll Anim Sci & Technol, Changchun, Peoples R China
基金
中国博士后科学基金;
关键词
Middle East respiratory syndrome; coronavirus; Receptor binding domain; CPV; Virus-like particles; Immune response; RESPIRATORY SYNDROME CORONAVIRUS; PARVOVIRUS-LIKE PARTICLES; NEUTRALIZING ANTIBODIES; SPIKE PROTEIN; CANINE PARVOVIRUS; NANOPARTICLES; INFECTION; EFFICACY; ANTIGEN;
D O I
10.1016/j.antiviral.2016.12.019
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-gamma, 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 (Thl) 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. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:55 / 61
页数:7
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