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PLoS One. 2015 Dec 7;10(12):e0144475. doi: 10.1371/journal.pone.0144475. eCollection 2015.

Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases.

Shi J1,2, Zhang J1,3, Li S1,2, Sun J1,2, Teng Y1,2, Wu M1,2, Li J1,2, Li Y1,2, Hu N1,2, Wang H1,2, Hu Y1,2.

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Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China.
Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, Hebei, China.


Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.

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