Bioinformatic analysis of B and T cell epitopes from SARS-CoV-2 Spike, Membrane and Nucleocapsid proteins as a strategy to assess possible cross-reactivity between emerging variants, including Omicron, and other human coronaviruses

  1. Diana Laura Pacheco-Olvera
  2. Stephanie Saint Remy-Hernández
  3. María Guadalupe García-Valeriano
  4. Tania Rivera-Hernández
  5. Constantino López-Macías

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Abstract

The COVID-19 pandemic caused by SARS-CoV-2 produced a global health emergency since December 2019, that up to the end of January 2022 had caused the death of more than 5.6 million people worldwide. Despite emergence of new variants of concern, vaccination remains one of the most important tools to control the pandemic. All approved vaccines and most of the vaccine candidates use the spike protein of the virus as a target antigen to induce protective immune responses. Several variants of the virus present key mutations in this protein which render the virus, at different rates, to evade the neutralizing antibody response. Although experimental evidence suggests that cross-reactive responses between coronaviruses are present in the population, it is unknown which potential antigens shared between different coronaviruses could be responsible for these responses. This study provides predictions of new potential B and T cell epitopes within SARS-CoV-2 Spike (S), Membrane (M) and Nucleocapsid (N) proteins together with a review of the reported B epitopes of these proteins. We also analyse amino acid changes present in the epitopes of variants of concern (VOC) and variants being monitored (VBM), and how these might affect the immune response, as these changes may alter the peptides’ immunogenicity index and the antigen presentation by related HLA alleles. Finally, given these observations, we performed an identity analysis between the repertoire of potential epitopes of SARS-CoV-2 and other human coronaviruses to identify which are conserved among them.

The results shown here together with the published experimental evidence, allow us to support the hypothesis that antibody and T cell cross-reactive responses to common coronaviruses epitopes, could contribute to broaden the protective response to SARS-CoV-2 and its variants. This evidence could help not only to understand cross-reactive responses among coronaviruses but also contribute to elucidate their role in immunity to SARS-CoV-2 induced by infection and/or vaccination. Finally, these findings could promote targeted analysis of antigen-specific immune responses and might orient and drive the rational development of new SARS-CoV-2 vaccines including candidates that ideally provide “universal” protection against other coronaviruses relevant to human health.

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    SciScore for 10.1101/2022.02.16.480759: (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
    Once the nucleotide sequences were translated into protein, Jalview, Clustal Omega and Blast (https://blast.ncbi.nlm.nih.gov/Blast.cgi)28,42,43 were used to perform multiple alignments to compare the various sequences to the reference sequence of the SARS-CoV-2 virus (QHR63290.2).
    Jalview
    suggested: (Jalview, RRID:SCR_006459)
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    Molecular Graphics System (PyMOL) Version 1.80 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: We detected the following sentences addressing limitations in the study:
    The main limitation of this study is that the B cell epitopes prediction tools we used does not predict conformational epitopes. As well as the case of S protein, immunodominant epitopes have also been reported for SARS-CoV-2 M and N proteins. In patients with severe disease treated at the Intensive Care Unit (ICU), it has been found high IgG titers specific to S protein linear B cell epitopes TESNKKFLPFQQFGRDIA, PSKPSKRSFIEDLLFNK and N protein epitope NNAAIVLQLPQGTTLPKG59. Additionally, the N protein epitope mentioned above, has been associated with lymphopenia in patients with COVID-1989. These S and N epitopes have a low mutation rate (<2%) and could be used as markers for COVID-19 induced immunopathology89. Even though neutralizing antibody responses are involved in protection against COVID-19 induced by SARS-CoV-2 infection or vaccination, T cell immune responses have been identified as an extremely important component of immunity against COVID-19. A study in patients with mild and severe COVID-19 showed the presence of effector and central memory SARS-CoV-2-specific T cells, in particular, mild cases generated higher frequencies of cytokine-producing CD8+ T cells90. Strong memory-specific T cell responses to SARS-CoV-2 have also been detected in individuals who had mild and asymptomatic infections, in some cases in the absence of antibody responses91. Another study reported T cell responses specific to SARS-CoV-2 peptide stimulation in pre-pandemic samples, which sugges...

    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 page 29. 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.

    Results from scite Reference Check: We found no unreliable references.

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