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

被引:29
作者
Liu, Xinglong [1 ,2 ]
Qu, Linbing [1 ]
Ye, Xianmiao [1 ,3 ]
Yi, Changhua [1 ]
Zheng, Xuehua [1 ]
Hao, Mingli [2 ]
Su, Wan [2 ]
Yao, Zhipeng [4 ]
Chen, Peihai [4 ]
Zhang, Shengnan [1 ]
Feng, Yupeng [1 ]
Wang, Qian [1 ,3 ]
Yan, Qihong [1 ,3 ]
Li, Pingchao [1 ]
Li, Heying [1 ]
Li, Feng [5 ]
Pan, Weiqi [5 ]
Niu, Xuefeng [5 ]
Xu, Ruian [2 ]
Feng, Liqiang [1 ]
Chen, Ling [1 ,2 ,5 ]
机构
[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Labs Resp Dis, Guangzhou, Guangdong, Peoples R China
[2] Huaqiao Univ, Sch Biomed Sci, Quanzhou, Peoples R China
[3] Univ Chinese Acad Sci, Beijing, Peoples R China
[4] Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Anhui, Peoples R China
[5] Guangzhou Med Univ, Guangzhou Peoples Hosp 8, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
DENGUE VIRUS; DNA VACCINE; JAPANESE ENCEPHALITIS; T-CELLS; ANTIBODIES; EFFICACY; MICE; IMMUNOGENICITY; REPLICATION; CANDIDATES;
D O I
10.1038/s41541-018-0072-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
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页数:8
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