Using a Virion Assembly-Defective Dengue Virus as a Vaccine Approach
文献类型：期刊论文
| 作者 | Shi, Pei-Yong2,3,7,8; Fink, Katja6; Mackenzie, Jason4; Ambrose, Rebecca1,4; Zhang, Bo5; Zust, Roland6; Zou, Jing7,8; Xie, Xuping7,8; Shan, Chao7,8 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2018-11-01 |
| 卷号 | 92期号:21页码:20 |
| 关键词 | dengue virus flavivirus vaccine NS2A trans-complementation viral assembly |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.01002-18 |
| 英文摘要 | Dengue virus (DENV) is the most prevalent mosquito-transmitted viral pathogen in humans. The recently licensed dengue vaccine has major weaknesses. Therefore, there is an urgent need to develop improved dengue vaccines. Here, we report a virion assembly-defective DENV as a vaccine platform. DENV containing an amino acid deletion (K188) in nonstructural protein 2A (NS2A) is fully competent in viral RNA replication but is completely defective in virion assembly. When trans-complemented with wild-type NS2A protein, the virion assembly defect could be rescued, generating pseudoinfectious virus (PIVNS2A) that could initiate single-round infection. The trans-complementation efficiency could be significantly improved through selection for adaptive mutations, leading to high-yield PIVNS2A production, with titers of >10(7) infectious-focus units (IFU)/ml. Mice immunized with a single dose of PIVNS2A elicited strong T cell immune responses and neutralization antibodies and were protected from wild-type-virus challenge. Collectively, the results proved the concept of using assembly-defective virus as a vaccine approach. The study also solved the technical bottleneck in producing high yields of PIVNS2A vaccine. The technology could be applicable to vaccine development for other viral pathogens. IMPORTANCE Many flaviviruses are significant human pathogens that pose global threats to public health. Although licensed vaccines are available for yellow fever, Japanese encephalitis, tick-borne encephalitis, and dengue viruses, new approaches are needed to develop improved vaccines. Using dengue virus as a model, we developed a vaccine platform using a virion assembly-defective virus. We show that such an assembly-defective virus could be rescued to higher titers and infect cells for a single round. Mice immunized with the assembly-defective virus were protected from wild-type-virus infection. This vaccine approach could be applicable to other viral pathogens. |
| 资助项目 | Novartis Institutes for BioMedical Research ; McLaughlin Endowment at the University of Texas Medical Branch ; University of Texas STARs Award ; Kleberg Foundation Award ; UTMB CTSA[UL1TR-001439] ; NIH[AI127744] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000447139100013 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/5987]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Shi, Pei-Yong |
| 作者单位 | 1.AAHL, CSIRO Hlth & Biosecur, Geelong, Vic, Australia 2.Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA 3.Univ Texas Med Branch, Dept Phamarcol & Toxicol, Galveston, TX 77555 USA 4.Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia 5.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China 6.ASTAR, Singapore Immunol Network, Singapore, Singapore 7.Novartis Inst Trop Dis, Singapore, Singapore 8.Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA |
| 推荐引用方式 GB/T 7714 | Shi, Pei-Yong,Fink, Katja,Mackenzie, Jason,et al. Using a Virion Assembly-Defective Dengue Virus as a Vaccine Approach[J]. JOURNAL OF VIROLOGY,2018,92(21):20. |
| APA | Shi, Pei-Yong.,Fink, Katja.,Mackenzie, Jason.,Ambrose, Rebecca.,Zhang, Bo.,...&Shan, Chao.(2018).Using a Virion Assembly-Defective Dengue Virus as a Vaccine Approach.JOURNAL OF VIROLOGY,92(21),20. |
| MLA | Shi, Pei-Yong,et al."Using a Virion Assembly-Defective Dengue Virus as a Vaccine Approach".JOURNAL OF VIROLOGY 92.21(2018):20. |
入库方式： OAI收割
来源：武汉植物园
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