Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)

被引：12

作者：

Zhang, Ya-Nan ^{[1
]}

Li, Na ^{[1
]}

Zhang, Qiu-Yan ^{[1
]}

Liu, Jing ^{[1
]}

Zhan, Shun-Li ^{[2
]}

Gao, Lei ^{[2
]}

Zeng, Xiang-Yue ^{[1
]}

Yu, Fang ^{[1
]}

Zhang, Hong-Qing ^{[1
]}

Li, Xiao-Dan ^{[1
]}

Deng, Cheng-Lin ^{[1
]}

Shi, Pei-Yong ^{[3
]}

Yuan, Zhi-Ming ^{[1
]}

Yuan, Shao-Peng ^{[2
]}

Ye, Han-Qing ^{[1
]}

Zhang, Bo ^{[1
]}

机构：

[1] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Peoples R China

[2] Beijing Shunlei Biotechnol Co Ltd, Beijing, Peoples R China

[3] Univ Texas Med Branch, Galveston, TX 77555 USA

来源：

EMBO MOLECULAR MEDICINE | 2021年 / 13卷 / 09期

关键词：

flavivirus; internal poly(A); live-attenuated vaccine; UTR; West Nile Virus; CIS-ACTING ELEMENTS; DENGUE VIRUS; 3'-UNTRANSLATED REGION; ENCEPHALITIS-VIRUS; ZIKA VIRUS; STRUCTURE DUPLICATIONS; UNTRANSLATED REGION; SECONDARY STRUCTURE; RNA; REPLICATION;

D O I：

10.15252/emmm.202114108

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The genus Flavivirus comprises numerous emerging and re-emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live-attenuated vaccine (LAV), WNV-poly(A), by replacing 5MODIFIER LETTER PRIME portion (corresponding to SL and DB domains in WNV) of 3MODIFIER LETTER PRIME-UTR with internal poly(A) tract. WNV-poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single-dose vaccination elicited robust and long-lasting immune responses, conferring full protection against WNV challenge. Such "poly(A)" vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.

引用

页数：12

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