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

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.

• Authors: Jiandong Shi, Jing Zhang, Sijin Li, Jing Sun, Yumei Teng, Meini Wu, Jianfan Li, Yanhan Li, Ningzhu Hu, Haixuan Wang, Yunzhang Hu
• Journal: PloS one (PLoS One) Vol. 10 Issue 12 Pg. e0144475 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26641892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Epitopes, B-Lymphocyte
• Epitopes, T-Lymphocyte
• Nucleocapsid Proteins
• Spike Glycoprotein, Coronavirus
• Viral Vaccines

Topics

• Antibodies, Neutralizing (immunology)
• Coronavirus Infections (immunology, virology)
• Epitopes, B-Lymphocyte (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Immunity, Cellular (immunology)
• Middle East Respiratory Syndrome Coronavirus (immunology)
• Nucleocapsid Proteins (immunology)
• Spike Glycoprotein, Coronavirus (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Viral Vaccines (immunology)