Abstract
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.
Highlights
Middle East respiratory syndrome (MERS) is a newly emerging acute respiratory system infectious disease, which is characterised by acute pneumonia, respiratory failure, and renal failure and caused by MERS-coronavirus (MERS-CoV) [1,2]
The 3D structure showed a maximum of 64% identity of the N protein of MERS-CoV with the best template protein PDB: 2ofzA (RNA Binding Domain of Sars Nucleocapsid Protein), and it is composed of two separate domains or pockets (Fig 2)
The domain-1 possessed the greater ability to interact with other proteins than the domain-2. This might be associated with distribution of the conformational epitopes on the N protein of MERS-CoV
Summary
Middle East respiratory syndrome (MERS) is a newly emerging acute respiratory system infectious disease, which is characterised by acute pneumonia, respiratory failure, and renal failure and caused by MERS-coronavirus (MERS-CoV) [1,2]. MERS-CoV was first isolated and identified in Saudi Arabia in 2012 as a new member in the lineage C of the genus Betacoronavirus, and is a zoonotic virus that is transmitted from bats to camels, and to humans [3,4,5]. The genome of MERS-CoV is a non-segmented positive-sense, single-stranded RNA (ssRNA) of approximately 30 kb encoding 11 proteins. They include two replicase polyproteins (open reading frames 1ab and 1a); four structural proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins; and five nonstructural proteins (open reading frames 3, 4a, 4b, 5, and 8b) [6].
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