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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1450114

M Protein Ectodomain-specific Immunity Restrains SARS-CoV-2 Variants Replication

Provisionally accepted
Yibo Tang Yibo Tang 1Kaiming Tang Kaiming Tang 2Yunqi Hu Yunqi Hu 3Zi-Wei Ye Zi-Wei Ye 2Wanyu Luo Wanyu Luo 3Cuiting Luo Cuiting Luo 2Hehe Cao Hehe Cao 2Ran Wang Ran Wang 4Xinyu Yue Xinyu Yue 3Dejian Liu Dejian Liu 1Cuicui Liu Cuicui Liu 1Xing-Yi Ge Xing-Yi Ge 1Tianlong Liu Tianlong Liu 5Chen Yao-Qing Chen Yao-Qing 3*Shuofeng Yuan Shuofeng Yuan 2*Lei Deng Lei Deng 1*
  • 1 College of Biology, Hunan University, Changsha, China
  • 2 The University of Hong Kong, Pokfulam, Hong Kong, SAR China
  • 3 School of Public Health, Sun Yat-sen University, Shenzhen Campus, Shenzhen, China
  • 4 Beijing Children’s Hospital, Capital Medical University, Beijing, Beijing Municipality, China
  • 5 China Agricultural University, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    The frequent occurrence of mutations in the SARS-CoV-2 Spike (S) protein, with up to dozens of mutations, poses a severe threat to the current efficacy of authorized COVID-19 vaccines. Membrane (M) protein, which is the most abundant viral structural protein, exhibits a high level of amino acid sequence conservation. M protein ectodomain could be recognized by specific antibodies; however, the extent to which it is immunogenic and provides protection remains unclear. Seroconversion rates for ectodomain-specific IgG were observed to be high in both SARS-CoV-2 convalescent patients and individuals immunized with inactivated vaccines. To assess the protective efficacy of the M protein ectodomain-based vaccine, we initially identified a highly immunogenic peptide derived from this ectodomain, named S2M2-30. The mouse serum specific to S2M2-30 showed inhibitory effects on the replication of SARS-CoV-2 variants in vitro. Immunizations of K18-hACE2-transgenic mice with the S2M2-30-keyhole limpet hemocyanin (KLH) vaccine significantly reduced the lung viral load caused by B.1.1.7/Alpha (UK) infection. Further mechanism investigations reveal that serum neutralizing activity, specific T-cell response and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) correlate with the specific immuno-protection conferred by S2M2-30. The findings of this study suggest that the antibody responses against M protein ectodomain in the population most likely exert a beneficial effect on preventing various SARS-CoV-2 infections.

    Keywords: SARS-CoV-2, membrane protein, Cross-inhibition, serum neutralizing activity, Antibody-dependent cellular cytotoxicity

    Received: 16 Jun 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Tang, Tang, Hu, Ye, Luo, Luo, Cao, Wang, Yue, Liu, Liu, Ge, Liu, Yao-Qing, Yuan and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Chen Yao-Qing, School of Public Health, Sun Yat-sen University, Shenzhen Campus, Shenzhen, China
    Shuofeng Yuan, The University of Hong Kong, Pokfulam, 999077, Hong Kong, SAR China
    Lei Deng, College of Biology, Hunan University, Changsha, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.