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Rational Design of SARS-CoV-2 Spike Glycoproteins To Increase Immunogenicity By T Cell Epitope Engineering

View ORCID ProfileEdison Ong, View ORCID ProfileXiaoqiang Huang, Robin Pearce, View ORCID ProfileYang Zhang, View ORCID ProfileYongqun He
doi: https://doi.org/10.1101/2020.08.14.251496
Edison Ong
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
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Xiaoqiang Huang
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
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Robin Pearce
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
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Yang Zhang
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
2Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
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  • For correspondence: zhng@umich.edu yongqunh@med.umich.edu
Yongqun He
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
3Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA
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  • For correspondence: zhng@umich.edu yongqunh@med.umich.edu
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Abstract

The current COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of confirmed cases and thousands of deaths globally. Extensive efforts and progress have been made to develop effective and safe vaccines against COVID-19. A primary target of these vaccines is the SARS-CoV-2 spike (S) protein, and many studies utilized structural vaccinology techniques to either stabilize the protein or fix the receptor-binding domain at certain states. In this study, we extended an evolutionary protein design algorithm, EvoDesign, to create thousands of stable S protein variants without perturbing the surface conformation and B cell epitopes of the S protein. We then evaluated the mutated S protein candidates based on predicted MHC-II T cell promiscuous epitopes as well as the epitopes’ similarity to human peptides. The presented strategy aims to improve the S protein’s immunogenicity and antigenicity by inducing stronger CD4 T cell response while maintaining the protein’s native structure and function. The top EvoDesign S protein candidate (Design-10705) recovered 31 out of 32 MHC-II T cell promiscuous epitopes in the native S protein, in which two epitopes were present in all seven human coronaviruses. This newly designed S protein also introduced nine new MHC-II T cell promiscuous epitopes and showed high structural similarity to its native conformation. The proposed structural vaccinology method provides an avenue to rationally design the antigen’s structure with increased immunogenicity, which could be applied to the rational design of new COVID-19 vaccine candidates.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 14, 2020.
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Rational Design of SARS-CoV-2 Spike Glycoproteins To Increase Immunogenicity By T Cell Epitope Engineering
Edison Ong, Xiaoqiang Huang, Robin Pearce, Yang Zhang, Yongqun He
bioRxiv 2020.08.14.251496; doi: https://doi.org/10.1101/2020.08.14.251496
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Rational Design of SARS-CoV-2 Spike Glycoproteins To Increase Immunogenicity By T Cell Epitope Engineering
Edison Ong, Xiaoqiang Huang, Robin Pearce, Yang Zhang, Yongqun He
bioRxiv 2020.08.14.251496; doi: https://doi.org/10.1101/2020.08.14.251496

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