PMID- 35095907 OWN - NLM STAT- MEDLINE DCOM- 20220209 LR - 20230228 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2. PG - 812176 LID - 10.3389/fimmu.2021.812176 [doi] LID - 812176 AB - 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-Guerin (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. CI - Copyright (c) 2022 Tarabini, Rigo, Faustino Fonseca, Rubin, Belle, Kavraki, Ferreto, Amaral Antunes and de Souza. FAU - Tarabini, Renata Fioravanti AU - Tarabini RF AD - Laboratory of Clinical and Experimental Immunology, Infant Center, School of Health Science, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. FAU - Rigo, Mauricio Menegatti AU - Rigo MM AD - Kavraki Lab, Department of Computer Science, Rice University, Houston, TX, United States. FAU - Faustino Fonseca, Andre AU - Faustino Fonseca A AD - Antunes Lab, Department of Biology and Biochemistry, University of Houston, Houston, TX, United States. FAU - Rubin, Felipe AU - Rubin F AD - School of Technology - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. FAU - Belle, Rafael AU - Belle R AD - Laboratorio de alto desempenho - Centro de Apoio ao desenvolvimento cientifico e tecnologico da (IDEIA), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. FAU - Kavraki, Lydia E AU - Kavraki LE AD - Kavraki Lab, Department of Computer Science, Rice University, Houston, TX, United States. FAU - Ferreto, Tiago Coelho AU - Ferreto TC AD - School of Technology - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. AD - Laboratorio de alto desempenho - Centro de Apoio ao desenvolvimento cientifico e tecnologico da (IDEIA), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. FAU - Amaral Antunes, Dinler AU - Amaral Antunes D AD - Antunes Lab, Department of Biology and Biochemistry, University of Houston, Houston, TX, United States. FAU - de Souza, Ana Paula Duarte AU - de Souza APD AD - Laboratory of Clinical and Experimental Immunology, Infant Center, School of Health Science, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. LA - eng GR - U01 CA258512/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220113 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (BCG Vaccine) RN - 0 (Peptides) RN - 0 (Viral Vaccines) SB - IM MH - BCG Vaccine/*immunology MH - COVID-19/*immunology MH - Cross Reactions/*immunology MH - Humans MH - Pandemics/prevention & control MH - Peptides/*immunology MH - SARS-CoV-2/*immunology MH - T-Lymphocytes/*immunology MH - Vaccination/methods MH - Viral Vaccines/*immunology PMC - PMC8793865 OTO - NOTNLM OT - BCG OT - HLA OT - SARS-CoV-2 OT - cross-reactivity OT - peptide OT - structural bioinformatics OT - vaccine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/01 06:00 MHDA- 2022/02/10 06:00 PMCR- 2022/01/13 CRDT- 2022/01/31 05:56 PHST- 2021/11/09 00:00 [received] PHST- 2021/12/21 00:00 [accepted] PHST- 2022/01/31 05:56 [entrez] PHST- 2022/02/01 06:00 [pubmed] PHST- 2022/02/10 06:00 [medline] PHST- 2022/01/13 00:00 [pmc-release] AID - 10.3389/fimmu.2021.812176 [doi] PST - epublish SO - Front Immunol. 2022 Jan 13;12:812176. doi: 10.3389/fimmu.2021.812176. eCollection 2021.