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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.
Affiliation
  • Edison Ong; University of Michigan Medical School, Ann Arbor, MI 48109, USA
  • Xiaoqiang Huang; University of Michigan Medical School, Ann Arbor, MI 48109, USA
  • Robin Pearce; University of Michigan Medical School, Ann Arbor, MI 48109, USA
  • Yang Zhang; University of Michigan
  • Yongqun He; University of Michigan
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-251496
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 proteins immunogenicity and antigenicity by inducing stronger CD4 T cell response while maintaining the proteins 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 antigens structure with increased immunogenicity, which could be applied to the rational design of new COVID-19 vaccine candidates.
License
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Document type: Preprint
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Document type: Preprint