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MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques

2016; Impact Journals LLC; Volume: 8; Issue: 8 Linguagem: Inglês

10.18632/oncotarget.8475

1949-2553

Chong Wang, Xuexing Zheng, Weiwei Gai, Yongkun Zhao, Hualei Wang, Haijun Wang, Na Feng, Hang Chi, Boning Qiu, Nan Li, Tiecheng Wang, Yuwei Gao, Songtao Yang, Xianzhu Xia,

Viral Infections and Vectors

// Chong Wang 1, 2, * , Xuexing Zheng 2, 3, 4, * , Weiwei Gai 2, * , Yongkun Zhao 2, 4 , Hualei Wang 2, 4 , Haijun Wang 2 , Na Feng 2, 4 , Hang Chi 2 , Boning Qiu 2 , Nan Li 2 , Tiecheng Wang 2, 4 , Yuwei Gao 2, 4 , Songtao Yang 2, 4 Xianzhu Xia 2, 4 1 College of Wildlife Resources, Northeast Forestry University, Harbin, China 2 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China 3 School of Public Health, Shandong University, Jinan, China 4 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China * These authors have contributed equally to this work Correspondence to: Xianzhu Xia, e-mail: xiaxzh@cae.cn Songtao Yang, e-mail: yst62041@163.com Keywords: Middle East respiratory syndrome coronavirus, vaccine, virus-like particles, nonhuman primates, immune response Received: November 16, 2015 Accepted: March 14, 2016 Published: March 30, 2016 ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. A lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. In this study, we generated MERS-CoV VLPs using the baculovirus expression system. Electron microscopy and immunoelectron microscopy results demonstrate that MERS-CoV VLPs are structurally similar to the native virus. Rhesus macaques inoculated with MERS-CoV VLPs and Alum adjuvant induced virus-neutralizing antibodies titers up to 1:40 and induced specific IgG antibodies against the receptor binding domain (RBD), with endpoint titers reaching 1:1,280. MERS-CoV VLPs also elicited T-helper 1 cell (Th1)-mediated immunity, as measured by ELISpot. These data demonstrate that MERS-CoV VLPs have excellent immunogenicity in rhesus macaques, and represent a promising vaccine candidate.