{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:10:04Z","timestamp":1778199004712,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["COV20_00679 (MPY 222-20)"],"award-info":[{"award-number":["COV20_00679 (MPY 222-20)"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MPY 509\/19"],"award-info":[{"award-number":["MPY 509\/19"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MPY 388\/18"],"award-info":[{"award-number":["MPY 388\/18"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.<\/jats:p>","DOI":"10.3390\/ijms23062977","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"2977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana","family":"Tajuelo","sequence":"first","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-8446","authenticated-orcid":false,"given":"Mireia","family":"L\u00f3pez-Siles","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"M\u00e1s","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-7905","authenticated-orcid":false,"given":"Pilar","family":"P\u00e9rez-Romero","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Aguado","sequence":"additional","affiliation":[{"name":"Hospital Universitario \u201c12 de Octubre\u201d, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Briz","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Mart\u00edn-Galiano","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-5878","authenticated-orcid":false,"given":"Daniel","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102911","DOI":"10.1016\/j.ebiom.2020.102911","article-title":"Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity","volume":"58","author":"Amrun","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals","volume":"181","author":"Grifoni","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41590-020-00808-x","article-title":"SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition","volume":"22","author":"Nelde","year":"2021","journal-title":"Nat. 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