A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy | |
Wei, Jiangxue1,2; Li, Zhengjun1; Yang, Yanli1; Ma, Xiaowei3; An, Wenqi3; Ma, Guanghui1; Su, Zhiguo1; Zhang, Songping1 | |
刊名 | VACCINE |
2020-08-27 | |
卷号 | 38期号:38页码:5987-5996 |
关键词 | Influenza Vaccine Virus Like-particles Biomimetic Nucleoprotein M2e |
ISSN号 | 0264-410X |
DOI | 10.1016/j.vaccine.2020.07.015 |
英文摘要 | Here we present a biomimetic strategy towards an influenza vaccine design based on hepatitis B virus core virus-like particles (HBc VLP). To this end, a temperature-shift based encapsulation process based on analysis of the unique thermal-associated structural flexibility of HBc VLP nanocages was proposed and proved efficient for encapsulation of antigen inside the VLP. By displaying a matrix protein 2 ectodomain (M2e) antigen on the exterior of HBc VLP through genetic fusion, and encapsulate a conserved internal nucleoprotein (NP) antigen peptide inside the VLP, a biomimetic dual-antigen influenza vaccine with interior NP/exterior M2e was constructed. For comparison, another non-biomimetic dual-antigen vaccine with interior M2e/exterior NP, and other four VLP-based single-antigen vaccines with NP or M2e either being encapsulated inside or genetically displayed outside the VLP were also constructed. Upon intraperitoneal immunization in mice, the dual-antigen VLP influenza vaccine elicited both NP and M2e-specific antibodies, which were stronger than those elicited by the single-antigen vaccines. Most importantly, after a lethal challenge of H1N1 virus, the biomimetic dual-antigen vaccine conferred the mice 100% protection without noticeable body weight loss in the absence of any adjuvant. While the protective efficacy conferred by the non-biomimetic one was only 62.5%, accompanying 12.5% body weight loss in the immunized mice. Besides the high level of antigen-specific antibodies, more efficient formation of total germinal center (GC) B cells and a higher level of effector memory CD8(+) T cell population were observed in the biomimetic vaccine group, as compared with the non-biomimetic one. All these results demonstrate that VLP assembly and display of antigens in a biomimetic manner making this a promising strategy for the production of efficient universal vaccines to influenza and other rapidly emerging pathogens. (C) 2020 Elsevier Ltd. All rights reserved. |
资助项目 | National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[31970872] ; National Natural Science Foundation of China[21808226] |
WOS关键词 | Virus-like Particles ; Protective Efficacy ; Immunogenicity ; Nanoparticles ; Ectodomain ; Peptide ; Nucleoprotein ; Lymphocytes ; Epitopes ; Delivery |
WOS研究方向 | Immunology ; Research & Experimental Medicine |
语种 | 英语 |
出版者 | ELSEVIER SCI LTD |
WOS记录号 | WOS:000564257700004 |
资助机构 | National Natural Science Foundation of China |
内容类型 | 期刊论文 |
源URL | [http://ir.ipe.ac.cn/handle/122111/41972] |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Su, Zhiguo; Zhang, Songping |
作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Hualan Biol Engn Inc, Xinxiang 453003, Henan, Peoples R China |
推荐引用方式 GB/T 7714 | Wei, Jiangxue,Li, Zhengjun,Yang, Yanli,et al. A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy[J]. VACCINE,2020,38(38):5987-5996. |
APA | Wei, Jiangxue.,Li, Zhengjun.,Yang, Yanli.,Ma, Xiaowei.,An, Wenqi.,...&Zhang, Songping.(2020).A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy.VACCINE,38(38),5987-5996. |
MLA | Wei, Jiangxue,et al."A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy".VACCINE 38.38(2020):5987-5996. |
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