Liu Xinglong, Qu Linbing, Ye Xianmiao, Yi Changhua, Zheng Xuehua, Hao Mingli, Su Wan, Yao Zhipeng, Chen Peihai, Zhang Shengnan, Feng Yupeng, Wang Qian, Yan Qihong, Li Pingchao, Li Heying, Li Feng, Pan Weiqi, Niu Xuefeng, Xu Ruian, Feng Liqiang, Chen Ling
1State Key Laboratories of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
2School of Biomedical Sciences, Huaqiao University, Quanzhou, China.
NPJ Vaccines. 2018 Jul 24;3:29. doi: 10.1038/s41541-018-0072-6. eCollection 2018.
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.
寨卡病毒（ZIKV）疫苗的当前设计主要将包膜（E）视为主要靶抗原。非结构蛋白NS1很少被考虑。在此，我们构建了三种腺病毒载体疫苗，分别携带E（Ad2-E）、或与E一起的前膜/膜（prM/M）（Ad2-prME）、或除了与E一起的prM/M之外还携带NS1（Ad2-prME-NS1）。Ad2-prME诱导产生的针对ZIKV的中和抗体反应高于Ad2-E，这表明prM/M对免疫原性E的折叠很重要。最有趣的是，当将免疫血清添加到ZIKV感染的细胞中时，Ad2-prME-NS1引发了最佳的病毒抑制作用。在由母体免疫的母鼠所生的经ZIKV攻击的新生小鼠中，Ad2-prME-NS1在预防体重减轻、神经紊乱和病毒复制方面提供了最佳保护。Ad2-prME也提供了显著的保护作用，但效果不如Ad2-prME-NS1，而Ad2-E仅减轻了神经症状，但没有抑制病毒复制。我们的研究表明，除了prM/M和E之外，在ZIKV疫苗设计中还应考虑NS1。
