Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus
文献类型：期刊论文
| 作者 | Li, Na2,3; Zhang, Ya-Nan2,3; Deng, Cheng-Lin3; Shi, Pei-Yong1; Yuan, Zhi-Ming3; Zhang, Bo3 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2019-09-01 |
| 卷号 | 93期号:17页码:13 |
| 关键词 | flavivirus NS1 West Nile virus vaccine |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.00720-19 |
| 英文摘要 | We previously produced a replication-defective West Nile virus (WNV) lacking NS1 (WNV-Delta NS1) that could propagate at low levels (105 infectious units [IU]/ml) in a 293T cell line expressing wild-type (WT) NS1. This finding indicates the potential of developing WNV-Delta NS1 as a noninfectious vaccine. To explore this idea, we developed an NS1-expressing Vero cell line (Vero(NS1)) that significantly improved the yield of WNV-Delta NS1 (10(8) IU/ml). We evaluated the safety and efficacy of WNV-Delta NS1 in mice. WNV-Delta NS1 appeared to be safe, as no replicative virus was found in naive Vero cells after continuous culturing of WNV-Delta NS1 in Vero(NS1) cells for 15 rounds. WNV-Delta NS1 was noninfectious in mice, even when IFNAR(-/-) mice were administered a high dose of WNV-Delta NS1. Vaccination with a single dose of WNV-Delta NS1 protected mice from a highly lethal challenge with WT WNV. The antibody response against WNV correlated well with the protection of vaccinated mice. Our study demonstrates the potential of the NS1 trans complementation system as a new platform for flavivirus vaccine development. IMPORTANCE Many flaviviruses are significant human pathogens that frequently cause outbreaks and epidemics around the world. Development of novel vaccine platforms against these pathogens is a public health priority. Using WNV as a model, we developed a new vaccine platform for flaviviruses. WNV containing a NS1 deletion (WNV-Delta NS1) could be efficiently trans complemented in Vero cells that constitutively expressed WT NS1 protein. A single-dose immunization with WNV-Delta NS1 elicited robust immune responses in mice. The immunized animals were fully protected against pathogenic WNV infection. No adverse effects related to the WNV-Delta NS1 vaccination were observed. The results have demonstrated the potential of the NS1 complementation system as an alternative platform for flavivirus vaccine development, especially for highly pathogenic flaviviruses. |
| 资助项目 | National Key Research and Development Program of China[2016YFD0500400] ; National Natural Science Foundation of China[81572003] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000480712100018 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/8759]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Zhang, Bo |
| 作者单位 | 1.Univ Texas Med Branch, Galveston, TX 77555 USA 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Ctr Emerging Infect Dis, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Na,Zhang, Ya-Nan,Deng, Cheng-Lin,et al. Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus[J]. JOURNAL OF VIROLOGY,2019,93(17):13. |
| APA | Li, Na,Zhang, Ya-Nan,Deng, Cheng-Lin,Shi, Pei-Yong,Yuan, Zhi-Ming,&Zhang, Bo.(2019).Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus.JOURNAL OF VIROLOGY,93(17),13. |
| MLA | Li, Na,et al."Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus".JOURNAL OF VIROLOGY 93.17(2019):13. |
入库方式： OAI收割
来源：武汉植物园
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