Incorporation of NS1 and prM/M are important to confer effective protection of adenovirus-vectored Zika virus vaccine carrying E protein

Xinglong Liu,Wan Su,Xianmiao Ye,Yupeng Feng,Linbing Qu,Weiqi Pan,Feng Li,Heying Li,Pingchao Li,Changhua Yi,Xuehua Zheng,Rong Xu ,Peihai Chen,Xuefeng Niu,Zhipeng Yao,Qihong Yan,Mingang Hao ,Qian Wang,Liqiang Feng,Shengnan Zhang,Ling Chen

doi:10.1038/s41541-018-0072-6

Abstract

Current design of Zika virus (ZIKV) vaccine mainly considered envelope (E) as the major target antigen. Non-structural protein NS1 was seldom considered. Herein, we generated three adenovirus-vectored vaccines carrying E (Ad2-E), or premembrane/membrane (prM/M) with E (Ad2-prME), or NS1 in addition to prM/M with E (Ad2-prME-NS1). Ad2-prME induced higher neutralizing antibody response to ZIKV than Ad2-E, suggesting prM/M is important for the folding of immunogenic E. Most intriguingly, Ad2-prME-NS1 elicited the best viral inhibition when the immune sera were added to ZIKV-infected cells. In ZIKV-challenged neonatal mice born to maternally immunized dams, Ad2-prME-NS1 conferred the best protection in preventing weight loss, neurological disorders, and viral replication. Ad2-prME also conferred significant protection but was less effective than Ad2-prME-NS1, whereas Ad2-E only alleviated neurological symptoms but did not inhibit viral replication. Our study suggested that NS1 should be considered in the design of ZIKV vaccine in addition to prM/M and E.

Highlights

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus belonging to family flaviviridae
Three E1, E3 deleted, replication incompetent serotype 2 (Supplementary Fig. S2), further supporting the inhibitory effect adenoviruses, Ad2-E, Ad2-prME, and Ad2-prME-NS1 were con- of NS1-specific antibodies on ZIKV infection
The amino sequences of E protein, prM/M prME-NS1 immune sera, depletion of E-binding or NS1-binding protein, and NS1 protein were from ZIKV isolate 1_0080_PF antibodies significantly attenuated the inhibitory activity of ZIKV

Summary

Introduction

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus belonging to family flaviviridae. Since 2007, outbreaks of ZIKV infection have been continuously reported in many countries in the Americas and Southeast Asia.[1]. ZIKV infection only caused mild and self-limited symptoms.[1]. Severe neurological diseases including congenital malformations and Guillain-Barré syndrome have been observed in recent epidemics.[2]. Sexual transmission has been established, in addition to mosquito vectors.[1,2]. Theses unusual clinical outcomes and transmission routes have posed potential threats for global public health.[1].

Methods

Results

Conclusion