Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus.

Rui-Xue Ma,Liang Zhang,Lin-Feng Cheng,Fang-Lin Zhang,Fang Wang,Wei Ye,Xiao-Xiao Zhang,Qi-Kang Ying,Rong-Rong Liu,Tie-Jun Ma,Zhi-Kai Xu,Zi-Yu Liu,Xing-An Wu

doi:10.3389/fcimb.2016.00151

Rui-Xue Ma, Liang Zhang + Show 11 more

Open Access

https://doi.org/10.3389/fcimb.2016.00151

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Abstract

The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-Kb-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-Kb. Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-Kb-restricted CTL epitope with involvement in the host immune response to HTNV infection.

Highlights

Hantaan virus (HTNV), the prototype of the Hantavirus genus, is a rodent-borne pathogen that is the major causative agent of hemorrhagic fever with renal syndrome (HFRS; Abbott et al, 1999)
The T cell response is a critical element of naturally acquired immunity to control viral infection, including HTNV infection (Rasmuson et al, 2011)
This fact provided the theoretical basis for the development of HTNV peptide vaccines to fight infection by inducing specific T cell responses

Summary

Introduction

Hantaan virus (HTNV), the prototype of the Hantavirus genus, is a rodent-borne pathogen that is the major causative agent of hemorrhagic fever with renal syndrome (HFRS; Abbott et al, 1999). Several types of inactivated vaccines targeting the pathogens that cause HFRS have been licensed (Liu et al, 2016). These inactivated vaccines have many shortcomings, Identification of the HTNV-GP CTL-Epitope including poor immunogenicity, which hinders the production of neutralizing antibodies or cell-mediated immunity (Song et al, 1992), and the concern of safety when using inactivated vaccines, which may contain some infectious particles. What’s more, epitope based vaccine has other considerable advantages, including increased safety, the opportunity to engineer the epitopes rationally for increased potency and breadth, and the ability to focus the immune response on conserved epitopes CTL epitope-specific T cell immunity demonstrate to be a long-term approach immune strategy. A potent T cell-activating peptide vaccine based on the HTNV structural protein may be a promising method of disease control (Ma et al, 2013)

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