A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant

Cai He, Jingyun Yang, Weiqi Hong, Zimin Chen, Dandan Peng, Hong Lei, Aqu Alu, Xuemei He, Zhenfei Bi, Xiaohua Jiang, Guowen Jia, Yun Yang, Yanan Zhou, Wenhai Yu, Cong Tang, Qing Huang, Mengli Yang, Bai Li, Jingmei Li, Junbin Wang, Haiying Que, Li Chen, Wenyan Ren, Dandan Wan, Jiong Li, Wei Wang, Guobo Shen, Zhiwei Zhao, Li Yang, Jinliang Yang, Zhenling Wang, Zhaoming Su, Yuquan Wei, Xiaobo Cen, Yoshimasa Tanaka, Xiangrong Song (), Shuaiyao Lu (), Xiaozhong Peng (), Guangwen Lu () and Xiawei Wei ()
Additional contact information
Cai He: Sichuan University
Jingyun Yang: Sichuan University
Weiqi Hong: Sichuan University
Zimin Chen: Sichuan University
Dandan Peng: Sichuan University
Hong Lei: Sichuan University
Aqu Alu: Sichuan University
Xuemei He: Sichuan University
Zhenfei Bi: Sichuan University
Xiaohua Jiang: Sichuan University
Guowen Jia: Sichuan University
Yun Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Yanan Zhou: Chinese Academy of Medical Sciences and Peking Union Medical College
Wenhai Yu: Chinese Academy of Medical Sciences and Peking Union Medical College
Cong Tang: Chinese Academy of Medical Sciences and Peking Union Medical College
Qing Huang: Chinese Academy of Medical Sciences and Peking Union Medical College
Mengli Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Bai Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Jingmei Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Junbin Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Haiying Que: Sichuan University
Li Chen: Sichuan University
Wenyan Ren: Sichuan University
Dandan Wan: Sichuan University
Jiong Li: Sichuan University
Wei Wang: Sichuan University
Guobo Shen: Sichuan University
Zhiwei Zhao: Sichuan University
Li Yang: Sichuan University
Jinliang Yang: Sichuan University
Zhenling Wang: Sichuan University
Zhaoming Su: Sichuan University
Yuquan Wei: Sichuan University
Xiaobo Cen: Sichuan University
Yoshimasa Tanaka: Nagasaki University
Xiangrong Song: Sichuan University
Shuaiyao Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaozhong Peng: Chinese Academy of Medical Sciences and Peking Union Medical College
Guangwen Lu: Sichuan University
Xiawei Wei: Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.

Date: 2022
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DOI: 10.1038/s41467-022-33209-9

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