{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:51:39Z","timestamp":1768085499034,"version":"3.49.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"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>Background<\/jats:title><jats:p>Understanding the humoral immune response towards viral infection and vaccination is instrumental in developing therapeutic tools to fight and restrict the viral spread of global pandemics. Of particular interest are the specificity and breadth of antibody reactivity in order to pinpoint immune dominant epitopes that remain immutable in viral variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used profiling with peptides derived from the Spike surface glycoprotein of SARS-CoV-2 to compare the antibody reactivity landscapes between patients and different vaccine cohorts. Initial screening was done with peptide microarrays while detailed results and validation data were obtained using peptide ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, antibody patterns turned out to be individually distinct. However, plasma samples of patients conspicuously recognized epitopes covering the fusion peptide region and the connector domain of Spike S2. Both regions are evolutionarily conserved and are targets of antibodies that were shown to inhibit viral infection. Among vaccinees, we discovered an invariant Spike region (amino acids 657-671) N-terminal to the furin cleavage site that elicited a significantly stronger antibody response in AZD1222- and BNT162b2- compared to NVX-CoV2373-vaccinees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Understanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1192395","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T04:58:38Z","timestamp":1683262718000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts"],"prefix":"10.3389","volume":"14","author":[{"given":"Peter","family":"Lorenz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Steinbeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Mai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil C.","family":"Reisinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"M\u00fcller-Hilke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track covid-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the Chadox1 ncov-19 vaccine (Azd1222) against sars-Cov-2: an interim analysis of four randomised controlled trials in Brazil, south Africa, and the uk","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the Bnt162b2 mrna covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"New Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022483","article-title":"An mrna vaccine against sars-Cov-2 - preliminary report","volume":"383","author":"Jackson","year":"2020","journal-title":"New Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107659","article-title":"Safety and efficacy of nvx-Cov2373 covid-19 vaccine","volume":"385","author":"Heath","year":"2021","journal-title":"New Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2622-0","article-title":"Sars-Cov-2 mrna vaccine design enabled by prototype pathogen preparedness","volume":"586","author":"Corbett","year":"2020","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD015477","article-title":"Efficacy and safety of covid-19 vaccines","volume":"12","author":"Grana","year":"2022","journal-title":"Cochrane Database systematic Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41541-021-00336-1","article-title":"Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against sars-Cov-2","volume":"6","author":"McDonald","year":"2021","journal-title":"NPJ Vaccines"},{"key":"B9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12916-021-02055-9","article-title":"Humoral immune responses during sars-Cov-2 mrna vaccine administration in seropositive and seronegative individuals","volume":"19","author":"Fraley","year":"2021","journal-title":"BMC Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.3390\/vaccines9121419","article-title":"Comirnaty-elicited and convalescent sera recognize different spike epitopes","volume":"9","author":"Hein","year":"2021","journal-title":"Vaccines"},{"key":"B11","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":"B12","doi-asserted-by":"publisher","first-page":"eabd4250","DOI":"10.1126\/science.abd4250","article-title":"Viral epitope profiling of covid-19 patients reveals cross-reactivity and correlates of severity","volume":"370","author":"Shrock","year":"2020","journal-title":"Science"},{"key":"B13","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":"Emerging Microbes infections"},{"key":"B14","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/s41598-023-27810-1","article-title":"Linear epitope mapping of the humoral response against sars-Cov-2 in two independent African cohorts","volume":"13","author":"Vigan-Womas","year":"2023","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02240-4","article-title":"Single-dose sars-Cov-2 vaccinations with either Bnt162b2 or Azd1222 induce disparate Th1 responses and iga production","volume":"20","author":"Muller","year":"2022","journal-title":"BMC Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00527-4","article-title":"Who international standard for anti-Sars-Cov-2 immunoglobulin","volume":"397","author":"Kristiansen","year":"2021","journal-title":"Lancet"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10091563","article-title":"Vaccine-induced T-cell and antibody responses at 12 months after full vaccination differ with respect to omicron recognition","volume":"10","author":"Mai","year":"2022","journal-title":"Vaccines"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.05.010","article-title":"Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis","volume":"11","author":"Hecker","year":"2012","journal-title":"Autoimmun Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (Iedb): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh2315","article-title":"Defining variant-resistant epitopes targeted by sars-Cov-2 antibodies: a global consortium study","volume":"374","author":"Hastie","year":"2021","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2111199119","DOI":"10.1073\/pnas.2111199119","article-title":"Sars-Cov-2 spike engagement of Ace2 primes S2' site cleavage and fusion initiation","volume":"119","author":"Yu","year":"2022","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e73490","DOI":"10.7554\/eLife.73490","article-title":"Comprehensive characterization of the antibody responses to sars-Cov-2 spike protein finds additional vaccine-induced epitopes beyond those for mild infection","volume":"11","author":"Garrett","year":"2022","journal-title":"eLife"},{"key":"B23","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.molcel.2020.04.022","article-title":"A multibasic cleavage site in the spike protein of sars-Cov-2 is essential for infection of human lung cells","volume":"78","author":"Hoffmann","year":"2020","journal-title":"Mol Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03237-4","article-title":"Loss of furin cleavage site attenuates sars-Cov-2 pathogenesis","volume":"591","author":"Johnson","year":"2021","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00841-7","article-title":"Sars-Cov-2 variant biology: immune escape, transmission and fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4251","article-title":"Distinct conformational states of sars-Cov-2 spike protein","volume":"369","author":"Cai","year":"2020","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238089","article-title":"Identification of immunodominant linear epitopes from sars-Cov-2 patient plasma","volume":"15","author":"Farrera-Soler","year":"2020","journal-title":"PloS One"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe3354","article-title":"Ultrapotent human antibodies protect against sars-Cov-2 challenge Via multiple mechanisms","volume":"370","author":"Tortorici","year":"2020","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1016\/j.cell.2021.02.026","article-title":"Human neutralizing antibodies against sars-Cov-2 require intact fc effector functions for optimal therapeutic protection","volume":"184","author":"Winkler","year":"2021","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41467-020-20653-8","article-title":"Sars-Cov-2 spike glycoprotein vaccine candidate nvx-Cov2373 immunogenicity in baboons and protection in mice","volume":"12","author":"Tian","year":"2021","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe1502","article-title":"Structural analysis of full-length sars-Cov-2 spike protein from an advanced vaccine candidate","volume":"370","author":"Bangaru","year":"2020","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41541-021-00369-6","article-title":"Distinguishing features of current covid-19 vaccines: knowns and unknowns of antigen presentation and modes of action","volume":"6","author":"Heinz","year":"2021","journal-title":"NPJ Vaccines"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001265","article-title":"The landscape of antibody binding in sars-Cov-2 infection","volume":"19","author":"Heffron","year":"2021","journal-title":"PloS Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202049101","article-title":"Peptide microarray-based analysis of antibody responses to sars-Cov-2 identifies unique epitopes with potential for diagnostic test development","volume":"51","author":"Holenya","year":"2021","journal-title":"Eur J Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s42003-021-01743-9","article-title":"Immunoreactive peptide maps of sars-Cov-2","volume":"4","author":"Mishra","year":"2021","journal-title":"Commun Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.629185","article-title":"Sars-Cov-2 proteome-wide analysis revealed significant epitope signatures in covid-19 patients","volume":"12","author":"Schwarz","year":"2021","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e148855","DOI":"10.1172\/jci.insight.148855","article-title":"Epitope-specific antibody responses differentiate covid-19 outcomes and variants of concern","volume":"6","author":"Voss","year":"2021","journal-title":"JCI Insight"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq3773","article-title":"Broadly neutralizing antibodies target the coronavirus fusion peptide","volume":"377","author":"Dacon","year":"2022","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq2679","article-title":"Ace2-binding exposes the sars-Cov-2 fusion peptide to broadly neutralizing coronavirus antibodies","volume":"377","author":"Low","year":"2022","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj3321","article-title":"Broad betacoronavirus neutralization by a stem helix-specific human antibody","volume":"373","author":"Pinto","year":"2021","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abi9215","article-title":"A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against sars-Cov-2 infection","volume":"14","author":"Zhou","year":"2022","journal-title":"Sci Trans Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade0958","article-title":"Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the sars-Cov-2 spike glycoprotein","volume":"8","author":"Bianchini","year":"2023","journal-title":"Sci Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00784-3","article-title":"Broadly neutralizing antibodies to sars-Cov-2 and other human coronaviruses","volume":"23","author":"Chen","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ai.2022.07.001","article-title":"Antibody-mediated immunity to sars-Cov-2 spike","volume":"154","author":"Errico","year":"2022","journal-title":"Adv Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1024","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":"B46","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.immuni.2022.04.003","article-title":"Analysis of memory b cells identifies conserved neutralizing epitopes on the n-terminal domain of variant sars-Cov-2 spike proteins","volume":"55","author":"Wang","year":"2022","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3390\/vaccines10020322","article-title":"Higher sars-Cov-2 spike binding antibody levels and neutralization capacity 6 months after heterologous vaccination with Azd1222 and Bnt162b2","volume":"10","author":"Muller-Hilke","year":"2022","journal-title":"Vaccines"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1192395\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T12:53:40Z","timestamp":1683636820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1192395\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2023.1192395"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1192395","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]},"article-number":"1192395"}}