Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants

  1. Anni Ge
  2. Melissa Rioux
  3. Alyson A. Kelvin

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Abstract

Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.

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    SciScore for 10.1101/2021.03.25.437035: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Prediction of B cell epitopes across variants: Predicted B cell epitopes across spike variants were assessed using the DiscoTope 2.0 server (http://www.cbs.dtu.dk/services/DiscoTope/) [30].
    DiscoTope
    suggested: (DiscoTope, RRID:SCR_018530)
    The amino acid number and DiscoTope score were used to map variant B cell epitopes in RStudio (version 3.6.1) using the ggplot2 package (version 3.3.2)[31].
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    The T cell epitopes predicted for the Wuhan and variant SARS-CoV-2 were compared by filtering the data in RStudio using the tidyverse package (version 1.3.0) [34].
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    Variant spike glycosylation site analysis: Wild-type and variant amino acid sequences were uploaded to the NetNGlyc 1.0 server (http://www.cbs.dtu.dk/services/NetNGlyc/) [35] to assess potential N-linked glycosylation sites (Asn-Xaa-Ser/Thr sequons).
    NetNGlyc
    suggested: (NetNGlyc, RRID:SCR_001570)
    The predicted glycosylation sites across variants were modelled using PyMOL (The PyMOL Molecular Graphics System, Version 2.3.5, Schrödinger, LLC).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2021.03.25.437035v1 on bioRxiv