Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus

被引:93
作者
Wang, Yaling [1 ,2 ,3 ]
Xie, Yuping [3 ]
Luo, Jia [3 ]
Guo, Mengyu [1 ,2 ]
Hu, Xuhao [1 ,2 ,4 ]
Chen, Xi [1 ,2 ,11 ]
Chen, Ziwei [1 ,2 ,4 ]
Lu, Xinyi [1 ,2 ,4 ]
Mao, Lichun [1 ,2 ,4 ]
Zhang, Kai [8 ]
Wei, Liangnian [3 ,5 ]
Ma, Yunfei [3 ]
Wang, Ruixin [3 ]
Zhou, Jia [3 ,10 ]
He, Chunyan [3 ]
Zhang, Yufang [3 ]
Zhang, Ye [3 ]
Chen, Sisi [3 ]
Shen, Lijuan [10 ]
Chen, Yun [5 ]
Qiu, Nasha [1 ,2 ]
Liu, Ying [1 ,2 ]
Cui, Yanyan [9 ]
Liao, Guoyang [3 ]
Liu, Ye [3 ]
Chen, Chunying [1 ,2 ,4 ,6 ,7 ]
机构
[1] Chinese Acad Sci, Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
[2] Chinese Acad Sci, Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China
[3] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Kunming 650000, Yunnan, Peoples R China
[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[5] Nanjing Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Nanjing 211166, Jiangsu, Peoples R China
[6] GBA Natl Inst Nanotechnol Innovat, Guangzhou 510700, Guangdong, Peoples R China
[7] Chinese Acad Med Sci, Res Unit Nanosci & Technol, Beijing 100021, Peoples R China
[8] Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China
[9] Beijing Inst Technol, Sch Optoelect, Beijing Engn Res Ctr Mixed Real & Adv Display, Beijing 100081, Peoples R China
[10] Kunming Med Univ, Sch Basic Med Sci, Dept Pathol, Kunming 650500, Yunnan, Peoples R China
[11] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China
基金
中国国家自然科学基金;
关键词
CELLS; DNA; VACCINATION; DEFENSE; PATHWAY;
D O I
10.1016/j.nantod.2021.101139
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (similar to 270-fold) and live coronavirus (> 8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4+ and CD8+ T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways. (C) 2021 Elsevier Ltd. All rights reserved.
引用
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页数:11
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