Bioinformatic analysis of shared B and T cell epitopes amongst relevant coronaviruses to human health: Is there cross-protection?

  1. Diana Laura Pacheco-Olvera
  2. Stephanie Saint Remy-Hernández
  3. Ernesto Acevedo-Ochoa
  4. Lourdes Arriaga-Pizano
  5. Arturo Cérbulo-Vázquez
  6. Eduardo Ferat-Osorio
  7. Tania Rivera-Hernández
  8. Constantino López-Macías

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Abstract

Within the last 30 years 3 coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2, have evolved and adapted to cause disease and spread amongst the human population. From the three, SARS-CoV-2 has spread world-wide and to July 2020 it has been responsible for more than 11 million confirmed cases and over half a million deaths. In the absence of an effective treatment or vaccine, social distancing has been the most effective measure to control the pandemic. However it has become evident that as the virus spreads the only tool that will allow us to fully control it is an effective vaccine. There are currently more than 150 vaccine candidates in different stages of development using a variety of viral antigens, with the S protein being the most targeted antigen. Although some new experimental evidence suggests cross-reacting responses between coronaviruses are present in the population, it remains unknown whether potential shared antigens between different coronaviruses could provide cross-protection. Given that coronaviruses are emerging pathogens and continue to represent a threat to global health, the development of a SARS-Cov-2 vaccine that could provide ‘universal’ protection against other coronaviruses should be pushed forward. Here we present a thorough review of reported B and T cell epitopes shared between SARS-CoV-2 and other relevant coronaviruses, in addition we used web-based tools to predict novel B and T cell epitopes that have not been reported before. Analysis of experimental evidence that is constantly emerging complemented with the findings of this study allow us support the hypothesis that cross-reactive responses, particularly those coming from T cells, might play a key role in controlling infection by SARS-CoV-2. We hope that with the evidence presented in this manuscript we provide arguments to encourage the study of cross-reactive responses in order to elucidate their role in immunity to SARS-CoV-2. Finally we expect our findings will aid targeted analysis of antigen-specific immune responses and guide future vaccine design aiming to develop a cross reactive effective vaccine against respiratory diseases caused by coronaviruses.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.14.202887: (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
    Protein multiple sequence alignments were performed using Clustal Omega (
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    Prediction of conformational B cell epitopes was performed using the ElliPro and DiscoTope 2.0 tools from IEDB website (14, 15).
    DiscoTope
    suggested: (DiscoTope, RRID:SCR_018530)
    The 3D structures were built and analysed using PyMOL® software (Schrödinger LLC.
    PyMOL®
    suggested: (PyMOL, RRID:SCR_000305)
    Molecular Graphics System (PyMoL
    PyMoL
    suggested: (PyMOL, RRID:SCR_000305)
    The basic local alignment search tool online (https://blast.ncbi.nlm.nih.gov/Blast.cgi) was used to assess the position of the predicted peptides in the glycoprotein sequence.
    https://blast.ncbi.nlm.nih.gov/Blast.cgi
    suggested: (TBLASTX, RRID:SCR_011823)

    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: We detected the following sentences addressing limitations in the study:
    Even though ElliPro and DiscoTope yielded the prediction of epitopes in similar regions of the spike glycoprotein, there are limitations in the accuracy of these predictions given the nature of conformational epitopes. As more experimental data is generated, predictions of conformational epitopes for the SARS-CoV-2 spike glycoprotein will become more refined and precise. Despite the limitations, we believe that investigating potential neutralising antibodies against the predicted residues should be pursued. Given that coronaviruses have a latent pandemic potential we were interested to see if amongst the epitopes compiled in this manuscript there were conserved epitopes between the SARS-CoV-2 spike glycoprotein and other relevant human coronaviruses. We identified only 7 linear B cell epitopes that share certain identity between the SARS-CoV-2 spike glycoprotein and other coronaviruses. The percentages of identity between peptides ranged from 19 to 100%, with only one epitope with at least 60% identity between SARS-CoV-2 and all the other coronaviruses. Recent studies have shown that anti-spike antibodies generated in response to SARS-CoV infection recognise the spike glycoprotein of SARS-CoV-2 and vice versa, suggesting antigenic similarities between the spike glycoprotein of these two viruses. However, these cross reactive antibodies did not show any neutralising activity against other than the virus that caused the infection (30). Given that SARS-CoV and SARS-CoV-2 share t...

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 16, 17 and 15. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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 10.1101/2020.07.14.202887v1 on bioRxiv