{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:01:05Z","timestamp":1779296465975,"version":"3.51.4"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Although 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-Gu\u00e9rin (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<jats:italic>in silico<\/jats:italic>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 \u201cneighborhoods\u201d of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.<\/jats:p>","DOI":"10.3389\/fimmu.2021.812176","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T11:27:44Z","timestamp":1642073264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2"],"prefix":"10.3389","volume":"12","author":[{"given":"Renata Fioravanti","family":"Tarabini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio Menegatti","family":"Rigo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Faustino Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Bell\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia E","family":"Kavraki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago Coelho","family":"Ferreto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinler","family":"Amaral Antunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula Duarte","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"B1","volume-title":"Novel Coronavirus (COVID-19) Situation","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets Across Tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00720-9","article-title":"COVID-19 Vaccines: Where We Stand and Challenges Ahead","volume":"28","author":"Forni","year":"2021","journal-title":"Cell Death Differ"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2104974","article-title":"Effectiveness of the BNT162b2 Covid-19 Vaccine Against the B.1.1.7 and B.1.351 Variants","volume":"385","author":"Abu-Raddad","year":"2021","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2105000","article-title":"Vaccine Breakthrough Infections With SARS-CoV-2 Variants","volume":"384","author":"Hacisuleyman","year":"2021","journal-title":"N Engl J Med"},{"key":"B7","article-title":"Sur La Vaccination Pr\u00e9ventive Des Enfants Nouveau-N\u00e9s Contre La Tuberculose Par Le BCG","volume":"41","author":"Calmette","year":"1927","journal-title":"Ann Inst Pasteur (Paris)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/imr.12968","article-title":"Vyakarnam A. 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