T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine

Ran Wang,Zida Zhen,Na Gao,Hui Chen,Jing An,Yueqi Li,Na Wu,Baohua Hou,Dongying Fan,Lance Turtle

doi:10.1007/s00253-020-10710-z

Abstract

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related to mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection but did mediate antibody-dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that the SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue to develop a novel bivalent vaccine against both ZIKV and JEV.Key points• JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice.• T cell immunity rather than antibody mediated the cross-protection.• It provides important information in terms of ZIKV prevention or precaution.

Highlights

IntroductionZika virus (ZIKV) has caused devastating outbreaks of fetal congenital malformations in South and Central
Zika virus (ZIKV) has caused devastating outbreaks of fetal congenital malformations in South and CentralAmerica and transmitted in more than 70 countries, including many previously unaffected regions
Multiple cytokines can be produced under ZIKV antigen stimulation, it was unclear whether cellular immunity was indispensable or essential for the in vivo cross-reactive protection

Summary

Introduction

Zika virus (ZIKV) has caused devastating outbreaks of fetal congenital malformations in South and Central. America and transmitted in more than 70 countries, including many previously unaffected regions. ZIKV infection during pregnancy increases the risk of neurological disorders in newborns (Zhou et al 2019), such as microcephaly. In. Appl Microbiol Biotechnol (2020) 104:6779–6789 adults, ZIKV causes Guillain-Barré syndrome and other neurologic disorders (Mendez et al 2017). ZIKV is a member of the genus Flavivirus, family Flaviviridae, which contains more than 70 viruses. Mosquito-borne flaviviruses such as Japanese encephalitis (JE) virus (JEV), dengue virus (DENV), ZIKV, yellow fever virus (YFV), and West Nile virus pose a threat to half of the world population and cause significant public health impact in many developing countries (Guarner and Hale 2019)

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