An mRNA-based T-cell-inducing antigen strengthens COVID-19 vaccine against SARS-CoV-2 variants

Wanbo Tai, Shengyong Feng, Benjie Chai, Shuaiyao Lu, Guangyu Zhao, Dong Chen, Wenhai Yu, Liting Ren, Huicheng Shi, Jing Lu, Zhuming Cai, Mujia Pang, Xu Tan, Penghua Wang, Jinzhong Lin (), Qiangming Sun (), Xiaozhong Peng () and Gong Cheng ()
Additional contact information
Wanbo Tai: Shenzhen Bay Laboratory
Shengyong Feng: Tsinghua University
Benjie Chai: Tsinghua University
Shuaiyao Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Guangyu Zhao: Academy of Military Medical Sciences
Dong Chen: Wenzhou Medical University
Wenhai Yu: Chinese Academy of Medical Sciences and Peking Union Medical College
Liting Ren: Tsinghua University
Huicheng Shi: Tsinghua University
Jing Lu: Fudan University
Zhuming Cai: Shenzhen Bay Laboratory
Mujia Pang: Shenzhen Bay Laboratory
Xu Tan: Tsinghua University
Penghua Wang: the University of Connecticut Health Center
Jinzhong Lin: Fudan University
Qiangming Sun: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaozhong Peng: Chinese Academy of Medical Sciences and Peking Union Medical College
Gong Cheng: Tsinghua University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Herd immunity achieved through mass vaccination is an effective approach to prevent contagious diseases. Nonetheless, emerging SARS-CoV-2 variants with frequent mutations largely evaded humoral immunity induced by Spike-based COVID-19 vaccines. Herein, we develop a lipid nanoparticle (LNP)-formulated mRNA-based T-cell-inducing antigen, which targeted three SARS-CoV-2 proteome regions that enriched human HLA-I epitopes (HLA-EPs). Immunization of HLA-EPs induces potent cellular responses to prevent SARS-CoV-2 infection in humanized HLA-A*02:01/DR1 and HLA-A*11:01/DR1 transgenic mice. Of note, the sequences of HLA-EPs are highly conserved among SARS-CoV-2 variants of concern. In humanized HLA-transgenic mice and female rhesus macaques, dual immunization with the LNP-formulated mRNAs encoding HLA-EPs and the receptor-binding domain of the SARS-CoV-2 B.1.351 variant (RBDbeta) is more efficacious in preventing infection of SARS-CoV-2 Beta and Omicron BA.1 variants than single immunization of LNP-RBDbeta. This study demonstrates the necessity to strengthen the vaccine effectiveness by comprehensively stimulating both humoral and cellular responses, thereby offering insight for optimizing the design of COVID-19 vaccines.

Date: 2023
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DOI: 10.1038/s41467-023-38751-8

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