Identification of Cytotoxic T Lymphocyte Epitopes on Swine Viruses: Multi-Epitope Design for Universal T Cell Vaccine

Yu-Chieh Liao,Chieh-Hua Lin,Hsin-Hung Lin,Wen-Bin Chung,Xiang-Jin Meng

doi:10.1371/journal.pone.0084443

Abstract

Classical swine fever (CSF), foot-and-mouth disease (FMD) and porcine reproductive and respiratory syndrome (PRRS) are the primary diseases affecting the pig industry globally. Vaccine induced CD8+ T cell-mediated immune response might be long-lived and cross-serotype and thus deserve further attention. Although large panels of synthetic overlapping peptides spanning the entire length of the polyproteins of a virus facilitate the detection of cytotoxic T lymphocyte (CTL) epitopes, it is an exceedingly costly and cumbersome approach. Alternatively, computational predictions have been proven to be of satisfactory accuracy and are easily performed. Such a method enables the systematic identification of genome-wide CTL epitopes by incorporating epitope prediction tools in analyzing large numbers of viral sequences. In this study, we have implemented an integrated bioinformatics pipeline for the identification of CTL epitopes of swine viruses including the CSF virus (CSFV), FMD virus (FMDV) and PRRS virus (PRRSV) and assembled these epitopes on a web resource to facilitate vaccine design. Identification of epitopes for cross protections to different subtypes of virus are also reported in this study and may be useful for the development of a universal vaccine against such viral infections among the swine population. The CTL epitopes identified in this study have been evaluated in silico and possibly provide more and wider protection in compared to traditional single-reference vaccine design. The web resource is free and open to all users through http://sb.nhri.org.tw/ICES.

Highlights

Classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV) and porcine reproductive and respiratory syndrome virus (PRRSV) are debilitating pathogens in the swine industry, resulting in serious economic losses year-afteryear
A schematic overview of the integrated bioinformatics pipeline depicted in Figure 1 was proposed to construct a web resource, named ICES, for the identification of the cytotoxic T lymphocytes (CTL) epitopes of swine viruses in this study
Available coding sequences of CSFV, FMDV, and PRRSV were all retrieved from NCBI GenBank

Summary

Introduction

Classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV) and porcine reproductive and respiratory syndrome virus (PRRSV) are debilitating pathogens in the swine industry, resulting in serious economic losses year-afteryear. The development of effective vaccines against these pathogens is of practical significance in the swine industry. Neutralizing antibodies induced upon vaccination are highly effective in controlling disease and viral transmission, they do not confer cross-subtype protection and might become ineffective due to antigenic changes [1]. The CTL epitope peptides could be used for the development of cross-protective human influenza vaccines, including recombinant viral vector and peptide vaccine [3,4,5]; the CTL epitope peptide identified for FMDV serotype O was cross-reactive to other FMDV serotypes [6]. Most of the analyses were restricted to specific viral proteins and were only able to identify few CTL epitopes

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Conclusion