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Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine
  • +12
  • Chaoyue Zhao,
  • Guonan Cai,
  • Shuai Jiang,
  • Xun Wang,
  • Chen Li,
  • Xinyu Liu,
  • Rui Qiao,
  • Xiaoyu Zhao,
  • Yuchen Cui,
  • Yanjia Chen,
  • Jiayan Li,
  • Changyi Liu,
  • Jizhen Yu,
  • Jiami Gong,
  • Pengfei Wang
Chaoyue Zhao
State Key Laboratory of Genetic Engineering at Fudan University
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Guonan Cai
State Key Laboratory of Genetic Engineering at Fudan University
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Shuai Jiang
State Key Laboratory of Genetic Engineering at Fudan University
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Xun Wang
State Key Laboratory of Genetic Engineering at Fudan University
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Chen Li
State Key Laboratory of Genetic Engineering at Fudan University
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Xinyu Liu
State Key Laboratory of Genetic Engineering at Fudan University
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Rui Qiao
State Key Laboratory of Genetic Engineering at Fudan University
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Xiaoyu Zhao
State Key Laboratory of Genetic Engineering at Fudan University
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Yuchen Cui
State Key Laboratory of Genetic Engineering at Fudan University
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Yanjia Chen
State Key Laboratory of Genetic Engineering at Fudan University
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Jiayan Li
State Key Laboratory of Genetic Engineering at Fudan University
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Changyi Liu
State Key Laboratory of Genetic Engineering at Fudan University
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Jizhen Yu
State Key Laboratory of Genetic Engineering at Fudan University
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Jiami Gong
State Key Laboratory of Genetic Engineering at Fudan University
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Pengfei Wang
State Key Laboratory of Genetic Engineering at Fudan University

Corresponding Author:pengfei_wang@fudan.edu.cn

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Abstract

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigates the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the ‘Knob-into-Hole’ technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, demonstrated remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.
Submitted to Journal of Medical Virology
09 May 2024Assigned to Editor
09 May 2024Submission Checks Completed
09 May 2024Review(s) Completed, Editorial Evaluation Pending
22 Jul 20241st Revision Received
23 Jul 2024Submission Checks Completed
23 Jul 2024Assigned to Editor
23 Jul 2024Review(s) Completed, Editorial Evaluation Pending
23 Jul 2024Reviewer(s) Assigned
23 Aug 2024Editorial Decision: Revise Minor
26 Aug 20242nd Revision Received
26 Aug 2024Submission Checks Completed
26 Aug 2024Assigned to Editor
26 Aug 2024Review(s) Completed, Editorial Evaluation Pending
31 Aug 2024Editorial Decision: Accept