A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus
文献类型：期刊论文
| 作者 | Liu, Wenjun1,2; Sun, Lei1,2; Chen, Can1,2; Fan, Wenhui2; Li, Jing1,2; Zheng, Weinan2; Zhang, Shuang2; Yang, Limin2; Liu, Di2,3 |
| 刊名 | FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
 |
| 出版日期 | 2018-05-01 |
| 卷号 | 8页码:11 |
| 关键词 | Influenza A virus vero cell line NS1 interferon vaccine |
| ISSN号 | 2235-2988 |
| DOI | 10.3389/fcimb.2018.00127 |
| 英文摘要 | Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3-6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-alpha/beta production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN-sensitive vaccine virus and a stable Vero cell line expressing NS1 to propagate the IFN-sensitive vaccine virus. The IFN-deficient system is applicable for the manufacture of IFN-sensitive vaccine virus. |
| 资助项目 | National Key R&D Program of China[2017YFD051105] ; National Key R&D Program of China[2016YFD0500206] ; National Key R&D Program of China[2016YFC1200803] ; National Key R&D Program of China[2015BAD11B02] ; National Natural Science Foundation of China[31630079] ; National Natural Science Foundation of China[31572526] ; National Natural Science Foundation of China[31672531] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDPB0301] |
| WOS研究方向 | Immunology ; Microbiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000431200700001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/5226]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Liu, Wenjun; Sun, Lei |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Virol, CAS Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Wenjun,Sun, Lei,Chen, Can,et al. A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus[J]. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,2018,8:11. |
| APA | Liu, Wenjun.,Sun, Lei.,Chen, Can.,Fan, Wenhui.,Li, Jing.,...&Liu, Di.(2018).A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus.FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,8,11. |
| MLA | Liu, Wenjun,et al."A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus".FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 8(2018):11. |
入库方式： OAI收割
来源：武汉植物园
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