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Potential T-cell and B-cell Epitopes of 2019-nCoV

Ethan Fast, View ORCID ProfileRuss B. Altman, View ORCID ProfileBinbin Chen
doi: https://doi.org/10.1101/2020.02.19.955484
Ethan Fast
aNash, Menlo Park, CA, USA
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Russ B. Altman
bDepartment of Bioengineering, Stanford University, Stanford, CA, USA
cDepartment of Genetics, Stanford University, Stanford, CA, USA
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Binbin Chen
cDepartment of Genetics, Stanford University, Stanford, CA, USA
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Abstract

As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data.

Significance Statement The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

Footnotes

  • B.C. and E.F. designed the study and implemented the analysis pipeline, and drafted the manuscript. R.A. provided insights into structural biology and reviewed the manuscript.

  • Authors have no competing interests.

  • We added the Figure 6 and updated Figure 5 as new structural data of 2019-nCoV becomes available.

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-NC 4.0 International license.
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Posted March 18, 2020.
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Potential T-cell and B-cell Epitopes of 2019-nCoV
Ethan Fast, Russ B. Altman, Binbin Chen
bioRxiv 2020.02.19.955484; doi: https://doi.org/10.1101/2020.02.19.955484
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Potential T-cell and B-cell Epitopes of 2019-nCoV
Ethan Fast, Russ B. Altman, Binbin Chen
bioRxiv 2020.02.19.955484; doi: https://doi.org/10.1101/2020.02.19.955484

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