SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses

Chuncong Mo; Xiao Li; Qianying Wu; Ye Fan; Donglan Liu; Yuhui Zhu; Yujie Yang; Xiaohong Liao; Zhichao Zhou; Liling Zhou; Qiuru Li; Qiong Zhang; Wenkuan Liu; Rong Zhou; Xingui Tian

doi:10.1016/j.vaccine.2023.09.059

SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses

Vaccine. 2023 Oct 9:S0264-410X(23)01156-8. doi: 10.1016/j.vaccine.2023.09.059. Online ahead of print.

Authors

Chuncong Mo¹, Xiao Li², Qianying Wu², Ye Fan¹, Donglan Liu², Yuhui Zhu², Yujie Yang², Xiaohong Liao³, Zhichao Zhou², Liling Zhou², Qiuru Li³, Qiong Zhang³, Wenkuan Liu², Rong Zhou⁴, Xingui Tian⁵

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China.
² State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
³ Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China.
⁴ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China. Electronic address: zhourong@gird.cn.
⁵ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. Electronic address: xgtian@gzhmu.edu.cn.

PMID: 37821314
DOI: 10.1016/j.vaccine.2023.09.059

Abstract

New SARS-CoV-2 variants continue to prevail worldwide, and effective vaccines are needed to prevent an epidemic. mRNA vaccines are gradually being applied to the prevention and control of infectious diseases with significant safety and effectiveness. The spike (S) protein of SARS-CoV-2 is the main target of mRNA vaccine design, but the impact of the signal peptide (SP), transmembrane region (TM), and cytoplasmic tail (CT) on mRNA vaccine remains unclear. In this study, we constructed three forms of mRNA vaccines related to the S protein: full-length, deletion of the TM and CT, and simultaneous deletion of the SP, TM and CT, and compared their immunogenicity. Our experimental data show that full-length S protein and deletion of the TM and CT could effectively induce neutralizing antibody production in mice, while S protein without the SP and TM could not. This indicates that the S protein SP is necessary for the design of mRNA vaccine.

Keywords: SARS-CoV-2; Signal peptide; Transmembrane region; mRNA vaccine.