{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:36:30Z","timestamp":1782135390052,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Considering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG\/IgA neutralizing activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response. <\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1010105","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T17:11:00Z","timestamp":1672938660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape"],"prefix":"10.3389","volume":"13","author":[{"given":"Jamille Ramos","family":"Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar Manuel Remuzgo","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Rahal Guaragna","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhosiene Yukari","family":"Magawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela Pazotti","family":"Daher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysson Henrique","family":"Urbanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Justamante H\u00e4ndel","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen Andrade","family":"Arcuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Alves","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greyce Luri","family":"Sasahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana Xavier","family":"de Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Carlos Vieira Silva","family":"J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edison Luiz","family":"Durigon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Beatriz","family":"Boscardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Santoro","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Schechtman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder I.","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edecio","family":"Cunha-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Gadermaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Kalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f4nica","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keity Souza","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"Tai","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. vol. 41","author":"Huang","year":"2020","journal-title":"Acta Pharmacol Sin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108915","article-title":"Linear epitope landscape of the SARS-CoV-2 spike protein constructed from 1,051 COVID-19 patients","volume":"34","author":"Li","year":"2021","journal-title":"Cell Rep"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.037","article-title":"Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology","volume":"183","author":"Piccoli","year":"2020","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/all.15066","article-title":"Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes","volume":"77","author":"Gattinger","year":"2022","journal-title":"Allergy: Eur J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1815591","article-title":"Functional mapping of b-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population","volume":"9","author":"Yi","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0827","article-title":"Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail","volume":"369","author":"Hansen","year":"2020","journal-title":"Sci (1979)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2241","article-title":"A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2","volume":"368","author":"Wu","year":"2020","journal-title":"Sci (1979)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24435-8","article-title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","volume":"12","author":"Greaney","year":"2021","journal-title":"Nat Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.006","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"Garcia-Beltran","year":"2021","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2102017","article-title":"Neutralizing activity of BNT162b2-elicited serum","volume":"384","author":"Liu","year":"2021","journal-title":"New Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/trf.16065","article-title":"Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: Preliminary lessons from a voluntary convalescent donor program","volume":"60","author":"Wendel","year":"2020","journal-title":"Transfus (Paris)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.htct.2021.03.001","article-title":"Suggested guidelines for convalescent plasma therapy for the treatment of COVID-19","volume":"43","author":"de Santis","year":"2021","journal-title":"Hematol Transfus Cell Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: Improving sequence-based b-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-5-113","article-title":"MUSCLE: A multiple sequence alignment method with reduced time and space complexity","volume":"5","author":"Edgar","year":"2004","journal-title":"BMC Bioinf"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1101\/gr.849004","article-title":"WebLogo: A sequence logo generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera - a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.647934","article-title":"A structural landscape of neutralizing antibodies against SARS-CoV-2 receptor binding domain. vol. 12","author":"Niu","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.647934","article-title":"Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity","volume":"370","author":"Shrock","year":"2020","journal-title":"Sci (1979)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1101\/2022.09.15.507787","article-title":"Imprinted SARS-CoV-2 humoral immunity induces convergent omicron RBD evolution","author":"Cao","year":"2022","journal-title":"bioRxiv"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00974-0","article-title":"Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern","volume":"6","author":"Dupont","year":"2021","journal-title":"Nat Microbiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01290-3","article-title":"Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. vol. 397","author":"Wall","year":"2021","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008209117","article-title":"Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions","volume":"117","author":"Wang","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04386-2","article-title":"Broadly neutralizing antibodies overcome SARS-CoV-2 omicron antigenic shift","volume":"602","author":"Cameroni","year":"2022","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04385-3","article-title":"Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies","volume":"602","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03398-2","article-title":"Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7","volume":"593","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.00965-21","article-title":"High-resolution linear epitope mapping of the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 mRNA vaccine recipients","volume":"9","author":"Nitahara","year":"2021","journal-title":"Microbiol Spectr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.07.20125096","article-title":"Linear epitopes of SARS-CoV-2 spike protein elicit neutralizing antibodies in COVID-19 patients. vol. 17","author":"Li","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85202-9","article-title":"SARS-CoV-2-induced humoral immunity through b cell epitope analysis in COVID-19 infected individuals","volume":"11","author":"Yoshida","year":"2021","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85202-9","article-title":"Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies","volume":"27","author":"Chen","year":"2021","journal-title":"Nat Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.06.003","article-title":"Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species","volume":"54","author":"Wang","year":"2021","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03324-6","article-title":"mRNA vaccine-elicited antibodies to SRS-CoV-2 and circulating variants","volume":"592","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.98.6.641","article-title":"Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus","volume":"98","author":"Davenport","year":"1953","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.98.6.641","article-title":"Antibody responses to omicron BA.4\/BA.5 bivalent mRNA vaccine booster shot","author":"Wang","year":"2022","journal-title":"bioRxiv"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7120","DOI":"10.1038\/s41467-022-34400-8","article-title":"Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4\/5\/2.75 subvariants in BA.2 breakthrough infections","volume":"13","author":"Ju","year":"2022","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12929-022-00830-1","article-title":"A booster dose of Delta\u2009\u00d7\u2009Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against omicron and other SARS-CoV-2 variants","volume":"29","author":"Lee","year":"2022","journal-title":"J BioMed Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1010105\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T17:11:03Z","timestamp":1672938663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1010105\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2022.1010105"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1010105","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]},"article-number":"1010105"}}