Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss In Spike

Kamil Wnuk, Jeremi Sudol, Patricia Spilman, Patrick Soon-Shiong
doi: https://doi.org/10.1101/2022.03.18.484954
Kamil Wnuk
1ImmunityBio, Inc. 9920 Jefferson Blvd., Culver City, CA 90232, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kamil.wnuk@immunitybio.com
Jeremi Sudol
1ImmunityBio, Inc. 9920 Jefferson Blvd., Culver City, CA 90232, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia Spilman
1ImmunityBio, Inc. 9920 Jefferson Blvd., Culver City, CA 90232, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Soon-Shiong
1ImmunityBio, Inc. 9920 Jefferson Blvd., Culver City, CA 90232, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

To provide a unique global view of the relative potential for evasion of CD8+ and CD4+ T cells by SARS-CoV-2 lineages as they evolve over time, we performed a comprehensive analysis of predicted HLA-I and HLA-II binding peptides in spike (S) and nucleocapsid (N) protein sequences of all available SARS-CoV-2 genomes as provided by NIH NCBI at a bi-monthly interval between March and December of 2021. A data supplement of all B.1.1.529 (Omicron) genomes from GISAID in early December was also used to capture the rapidly spreading variant. A key finding is that throughout continued viral evolution and increasing rates of mutations occurring at T-cell epitope hotspots, protein instances with worst case binding loss did not become the most frequent for any Variant of Concern (VOC) or Variant of Interest (VOI) lineage; suggesting T-cell evasion is not likely to be a dominant evolutionary pressure on SARS-CoV-2. We also determined that throughout the course of the pandemic in 2021, there remained a relatively steady ratio of viral variants that exhibit conservation of epitopes in the N protein, despite significant potential for epitope loss in S relative to other lineages. We further localized conserved regions in N with high epitope yield potential, and illustrated HLA-I binding heterogeneity across the S protein consistent with empirical observations. Although Omicron’s high volume of mutations caused it to exhibit more epitope loss potential than most frequently observed versions of proteins in almost all other VOCs, epitope candidates across its most frequent N proteins were still largely conserved. This analysis adds to the body of evidence suggesting that N may have merit as an additional antigen to elicit immune responses to vaccination with increased potential to provide sustained protection against COVID-19 disease in the face of emerging variants.

Competing Interest Statement

Authors are employed by ImmunityBio, Inc

Footnotes

  • https://research.immunitybio.com/scov2_epitopes/

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-ND 4.0 International license.
Back to top
PreviousNext
Posted March 20, 2022.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss In Spike
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss In Spike
Kamil Wnuk, Jeremi Sudol, Patricia Spilman, Patrick Soon-Shiong
bioRxiv 2022.03.18.484954; doi: https://doi.org/10.1101/2022.03.18.484954
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss In Spike
Kamil Wnuk, Jeremi Sudol, Patricia Spilman, Patrick Soon-Shiong
bioRxiv 2022.03.18.484954; doi: https://doi.org/10.1101/2022.03.18.484954

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3513)
  • Biochemistry (7359)
  • Bioengineering (5338)
  • Bioinformatics (20305)
  • Biophysics (10034)
  • Cancer Biology (7763)
  • Cell Biology (11329)
  • Clinical Trials (138)
  • Developmental Biology (6443)
  • Ecology (9968)
  • Epidemiology (2065)
  • Evolutionary Biology (13346)
  • Genetics (9364)
  • Genomics (12598)
  • Immunology (7718)
  • Microbiology (19058)
  • Molecular Biology (7452)
  • Neuroscience (41104)
  • Paleontology (300)
  • Pathology (1233)
  • Pharmacology and Toxicology (2141)
  • Physiology (3171)
  • Plant Biology (6867)
  • Scientific Communication and Education (1275)
  • Synthetic Biology (1899)
  • Systems Biology (5320)
  • Zoology (1090)