Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters

Shaohong Chen; Xinghai Zhang; Yanfeng Yao; Shengdong Wang; Kangyin Li; Baoyue Zhang; Tianxi Ye; Li Chen; Yan Wu; Entao Li; Bichao Xu; Pei Zhang; Xia Chuai; Yong Ran; Rui Gong; Huajun Zhang; Sandra Chiu

doi:10.1016/j.virs.2024.09.005

December 2024

. doi: 10.1016/j.virs.2024.09.005

Citation: Shaohong Chen, Xinghai Zhang, Yanfeng Yao, Shengdong Wang, Kangyin Li, Baoyue Zhang, Tianxi Ye, Li Chen, Yan Wu, Entao Li, Bichao Xu, Pei Zhang, Xia Chuai, Yong Ran, Rui Gong, Huajun Zhang, Sandra Chiu. Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters .VIROLOGICA SINICA, 2024, 39(6) : 909-916. http://dx.doi.org/10.1016/j.virs.2024.09.005

基于铁蛋白的纳米颗粒尼帕病毒糖蛋白疫苗可在小鼠和仓鼠体内引起保护性免疫反应

陈少红 ^a,b ,
张醒海 ^a ,
姚艳丰 ^c ,
王升东 ^a,b ,
李康音 ^a,b ,
张保越 ^a,b ,
叶天玺 ^a,b ,
陈荔 ^a,b ,
吴燕 ^a ,
李恩涛 ^e,f ,
许碧超 ^d ,
张配 ^d ,
揣侠 ^a ,
冉勇 ^c ,
龚睿 ^a,, ,
张化俊 ^a,, ,
Sandra Chiu ^e,f,g,,

cstr: 32224.14.j.virs.2024.09.005

a. 武汉病毒研究所, 武汉 430062;
b. 中国科学院大学, 北京 100049;
c. 中国科学技术大学, 合肥 230027

通讯作者： 龚睿, gongr@wh.iov.cn; 张化俊, hjzhang@wh.iov.cn; Sandra Chiu, qiux@ustc.edu.cn
收稿日期： 2024-06-20
录用日期： 2024-09-11

摘要

尼帕病毒属于副粘病毒科，亨尼帕病毒属，是一种在东南亚流行的人畜共患病毒，能导致人类和动物患上严重的呼吸系统疾病和脑炎，其致死率高达75%。该病毒对世界公共卫生和全球生物安全造成了严重的威胁，但目前仍无针对该病毒的上市疫苗。因此本研究将尼帕病毒的可溶性糖蛋白G（sG）或糖蛋白G的头部区域（G_head) 作为抗原，通过spycatcher/spytag技术将抗原装载在铁蛋白纳米颗粒上，制备了两种基于铁蛋白的纳米颗粒疫苗（FeNP-sG 和 FeNP-G_head）。与sG或G_head亚单位疫苗相比，FeNP-sG 和 FeNP-G_head 在小鼠中能够诱导较强的体液免疫和细胞反应，而FeNP-sG 免疫组的效果优于FeNP-G_head 免疫组。研究结果进表明，sG 具有比 G_head 更好的抗原性，且纳米颗粒疫苗可以显着增强免疫原性。此外，用5μg FeNP-sG 疫苗免疫仓鼠2次后进行NiV的攻毒实验，该疫苗可对仓鼠提供100% 的保护。因此本研究的对于抗击NiV等新发传染病具有重要意义，有助于全球公共卫生领域更好地应对未来可能出现的疫情。
- 尼帕病毒
- , 铁蛋白纳米颗粒疫苗
- , 候选疫苗

Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters

Shaohong Chen ^a,b ,
Xinghai Zhang ^a ,
Yanfeng Yao ^c ,
Shengdong Wang ^a,b ,
Kangyin Li ^a,b ,
Baoyue Zhang ^a,b ,
Tianxi Ye ^a,b ,
Li Chen ^a,b ,
Yan Wu ^a ,
Entao Li ^e,f ,
Bichao Xu ^d ,
Pei Zhang ^d ,
Xia Chuai ^a ,
Yong Ran ^c ,
Rui Gong ^a,, ,
Huajun Zhang ^a,, ,
Sandra Chiu ^e,f,g,,

a. CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430062, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China;
c. Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
d. Institutional Center for Shared Technologies and Facilities of Wuhan Institute of Virology, CAS, Center for Instrumental Analysis and Metrology, Wuhan 430062, China;
e. Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China;
f. Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei 230027, China;
g. Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China

Corresponding author: Rui Gong, gongr@wh.iov.cn Huajun Zhang, hjzhang@wh.iov.cn Sandra Chiu, qiux@ustc.edu.cn
Received Date: 20 June 2024
Accepted Date: 11 September 2024

Abstract

Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and G_head (residues 182-602, FeNP-G_head) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-G_head, respectively) through Spycatcher/Spytag technology. Compared with sG and G_head alone, FeNP-sG and FeNP-G_head elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-G_head group. These results further demonstrate that sG possesses greater antigenicity than G_head and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 μg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.
- Nipah virus (NiV)
- , Ferritin nanoparticles
- , Vaccine candidate

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Electronic Supplementary Material

10.1016j.virs.2024.09.005-ESM.docx