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A novel circular Delta-XBB.1.5 RBD dimeric protein subunit vaccine mediated by split intein elicits an immune response and protection against multiple SARS-CoV-2 variants in mice
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  • Kangyin Li,
  • Yan Wu,
  • Hongqing Zhang,
  • Shaohong Chen,
  • Bihao Wu,
  • Tingting Li,
  • Entao Li,
  • Feiyang Luo,
  • Aishun Jin,
  • Bo Zhang,
  • Yanan Zhang,
  • Rui Gong,
  • Huajun Zhang,
  • Sandra Chiu
Kangyin Li
Chinese Academy of Sciences Wuhan Institute of Virology
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Yan Wu
Chinese Academy of Sciences Wuhan Institute of Virology
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Hongqing Zhang
Chinese Academy of Sciences Wuhan Institute of Virology
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Shaohong Chen
Chinese Academy of Sciences Wuhan Institute of Virology
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Bihao Wu
Chinese Academy of Sciences Wuhan Institute of Virology
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Tingting Li
Chongqing Medical University
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Entao Li
University of Science and Technology of China Faculty of Life Sciences and Medicine
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Feiyang Luo
Chongqing Medical University
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Aishun Jin
Chongqing Medical University
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Bo Zhang
Chinese Academy of Sciences Wuhan Institute of Virology
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Yanan Zhang
Chinese Academy of Sciences Wuhan Institute of Virology
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Rui Gong
Chinese Academy of Sciences Wuhan Institute of Virology
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Huajun Zhang
Chinese Academy of Sciences Wuhan Institute of Virology

Corresponding Author:hjzhang@wh.iov.cn

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Sandra Chiu
University of Science and Technology of China Faculty of Life Sciences and Medicine
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Abstract

SARS-CoV-2 continues to mutate, leading to breakthrough infections. The development of new vaccine strategies to combat variant strains is crucial. Protein cyclization can enhance thermal stability and may improve immunogenicity. Here, we designed a cyclic tandem dimeric receptor-binding domain protein (cirRBD2) using the split intein Cth-Ter. Cyclization does not affect the antigen epitopes of the RBD but results in better thermal stability than that of its linear counterpart (linRBD2). Compared with those immunized with linRBD2, mice immunized with two doses of 5 μg of cirRBD2 produced significantly greater levels of broad-spectrum neutralizing antibodies than those immunized with linRBD2 and generated a considerable cellular immune response. In the VEEV-VRP-hACE2-transduced mouse model, two doses of 5 μg of cirRBD2 provided protection against infection with BA.5, XBB.1.9, and partial against EG.5 which has more mutations. This study developed a novel circular RBD dimer subunit vaccine for SARS-CoV-2 that exhibits broad-spectrum neutralizing activity against various variants. A similar strategy can be applied to develop vaccines for other pathogens, especially for thermally stable vaccines.
05 Aug 2024Submitted to Journal of Medical Virology
06 Aug 2024Submission Checks Completed
06 Aug 2024Assigned to Editor
06 Aug 2024Review(s) Completed, Editorial Evaluation Pending
06 Aug 2024Reviewer(s) Assigned
13 Sep 2024Editorial Decision: Revise Minor
29 Oct 20241st Revision Received
29 Oct 2024Submission Checks Completed
29 Oct 2024Assigned to Editor
29 Oct 2024Review(s) Completed, Editorial Evaluation Pending
04 Nov 2024Reviewer(s) Assigned