Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2

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dc.citation.articleNumber812176en_US
dc.citation.journalTitleFrontiers in Immunologyen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorTarabini, Renata Fioravantien_US
dc.contributor.authorRigo, Mauricio Menegattien_US
dc.contributor.authorFaustino Fonseca, Andréen_US
dc.contributor.authorRubin, Felipeen_US
dc.contributor.authorBellé, Rafaelen_US
dc.contributor.authorKavraki, Lydia E.en_US
dc.contributor.authorFerreto, Tiago Coelhoen_US
dc.contributor.authorAmaral Antunes, Dinleren_US
dc.contributor.authorde Souza, Ana Paula Duarteen_US
dc.contributor.orgKavraki Laben_US
dc.date.accessioned2022-03-24T13:31:41Zen_US
dc.date.available2022-03-24T13:31:41Zen_US
dc.date.issued2022en_US
dc.description.abstractAlthough not being the first viral pandemic to affect humankind, we are now for the first time faced with a pandemic caused by a coronavirus. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the COVID-19 pandemic, which caused more than 4.5 million deaths worldwide. Despite unprecedented efforts, with vaccines being developed in a record time, SARS-CoV-2 continues to spread worldwide with new variants arising in different countries. Such persistent spread is in part enabled by public resistance to vaccination in some countries, and limited access to vaccines in other countries. The limited vaccination coverage, the continued risk for resistant variants, and the existence of natural reservoirs for coronaviruses, highlight the importance of developing additional therapeutic strategies against SARS-CoV-2 and other coronaviruses. At the beginning of the pandemic it was suggested that countries with Bacillus Calmette-Guérin (BCG) vaccination programs could be associated with a reduced number and/or severity of COVID-19 cases. Preliminary studies have provided evidence for this relationship and further investigation is being conducted in ongoing clinical trials. The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells. In order to identify potential targets of T cell cross-reactivity, we implemented an in silico strategy combining sequence-based and structure-based methods to screen over 13,5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. Our study produced (i) a list of immunogenic BCG-derived peptides that may prime T cell cross-reactivity against SARS-CoV-2, (ii) a large dataset of modeled peptide-HLA structures for the screened targets, and (iii) new computational methods for structure-based screenings that can be used by others in future studies. Our study expands the list of BCG peptides potentially involved in T cell cross-reactivity with SARS-CoV-2-derived peptides, and identifies multiple high-density “neighborhoods” of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.en_US
dc.identifier.citationTarabini, Renata Fioravanti, Rigo, Mauricio Menegatti, Faustino Fonseca, André, et al.. "Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2." <i>Frontiers in Immunology,</i> 12, (2022) Frontiers Media S.A.: https://doi.org/10.3389/fimmu.2021.812176.en_US
dc.identifier.digitalfimmu-12-812176en_US
dc.identifier.doihttps://doi.org/10.3389/fimmu.2021.812176en_US
dc.identifier.urihttps://hdl.handle.net/1911/112043en_US
dc.language.isoengen_US
dc.publisherFrontiers Media S.A.en_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleLarge-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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