Japanese Encephalitis Virus Vaccination Elicits Cross-Reactive HLA-Class I-Restricted CD8 T Cell Response Against Zika Virus Infection.

Marion Tarbe,Jincun Zhao,Xianyang Chen,Wei Dong,Xiuzhen Li,Solene Grayo,Qibin Leng,Yongfen Xu,Jing Sun,Chengfeng Qin,Guang Hu,Li Liu

doi:10.3389/fimmu.2020.577546

Abstract

Japanese encephalitis virus (JEV) exposure or vaccination could elicit cross-reactive CD8 T cell immunity against heterologous flaviviruses in humans. In addition, cross-reactive CD8 T cells induced by dengue virus (DENV) have been shown to play a protective role against Zika virus (ZIKV). However, how JEV exposure or vaccination affects ZIKV infection in humans remains unclear. In this report, epitope prediction algorithms were used to predict the cross-reactive CD8 T cell epitope restricted to human HLA between JEV and ZIKV. We found that these predicted CD8 T cell epitopes are immunogenic and cross-reactive in humanized HLA transgenic mice. Moreover, JEV vaccine immunization provided cross-protection against ZIKV infection. Furthermore, CD8 T cells were involved in the protection against ZKIV infection in vivo. Our results have an important clinical implication that vaccination with JEV SA14-14-2 may provide protection against ZIKV infection in humans.

Highlights

Zika virus (ZIKV) is a global health threat due to its association with severe congenital malformations and its widespread transmission [1, 2]
As Japanese encephalitis virus (JEV) SA14-14-2 and ZIKV polyproteins share 56% sequence homology, we wondered whether JEV vaccination could induce cross-reactive CD8 T cell response against ZIKV infection in humans
To determine the potential JEV/ZIKV cross-reactive epitope restricted to human MHC-I, we predicted antigenic peptides from the JEV SA14-14-2 polyprotein using Immune Epitope Database Analysis Resource (IEDAR) software and selected candidates presenting IEDAR scores under 4, thereby obtaining 196, 185, 207, and 184 epitopes restricted to Human leukocyte antigen (HLA) B58, HLA A2, HLA A11, and HLA A24, respectively

Summary

INTRODUCTION

Zika virus (ZIKV) is a global health threat due to its association with severe congenital malformations and its widespread transmission [1, 2]. Recent studies have revealed that murine MHC I-restricted CD8 T cells from mice infected with JEV or vaccine strain are cross-reactive with ZIKV [18, 19]. These evidences suggest JEV vaccination may elicit cross-reactive T cell immunity against ZIKV and thereby affect ZIKV pathogenesis in humans. To test this hypothesis, we performed bioinformatic analysis to predict the cross-reactive epitope between JEV and ZIKV. Our results imply that JEV vaccination has a potential to protect ZIKV infection in humans by cross-reactive CD8 T cell immunity against these epitopes

RESULTS

DISCUSSION

MATERIALS AND METHODS

ETHICS STATEMENT