{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:31:32Z","timestamp":1784381492294,"version":"3.55.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saxon State Ministry for Science, Culture and Tourism"},{"DOI":"10.13039\/501100003185","name":"Fraunhofer Gesellschaft","doi-asserted-by":"crossref","award":["Defend-CoV2"],"award-info":[{"award-number":["Defend-CoV2"]}],"id":[{"id":"10.13039\/501100003185","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Virus Archive GLOBAL","award":["871029"],"award-info":[{"award-number":["871029"]}]},{"name":"Jeffrey Modell Foundation for Primary immunodeficiency diseases"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The currently used SARS-CoV-2 mRNA vaccines have proven to induce a strong and protective immune response. However, functional relevance of vaccine-generated antibodies and their temporal progression are still poorly understood. Thus, the central aim of this study is to gain a better understanding of systemic and mucosal humoral immune response after mRNA vaccination with BNT162b2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared antibody production against the S1 subunit and the RBD of the SARS-CoV-2 spike protein in sera of BNT162b2 vaccinees, heterologous ChAdOx1-S\/BNT162b2 vaccinees and COVID-19 patients. We monitored the neutralizing humoral response against SARS-CoV-2 wildtype strain and three VOCs over a period of up to eight months after second and after a subsequent third vaccination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In comparison to COVID-19 patients, vaccinees showed higher or similar amounts of S1- and RBD-binding antibodies but similar or lower virus neutralizing titers. Antibodies peaked two weeks after the second dose, followed by a decrease three and eight months later. Neutralizing antibodies (nAbs) poorly correlated with S1-IgG levels but strongly with RBD-IgGAM titers. After second vaccination we observed a reduced vaccine-induced neutralizing capacity against VOCs, especially against the Omicron variant. Compared to the nAb levels after the second vaccination, the neutralizing capacity against wildtype strain and VOCs was significantly enhanced after third vaccination. In saliva samples, relevant levels of RBD antibodies were detected in convalescent samples but not in vaccinees.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data demonstrate that BNT162b2 vaccinated individuals generate relevant nAbs titers, which begin to decrease within three months after immunization and show lower neutralizing potential against VOCs as compared to the wildtype strain. Large proportion of vaccine-induced S1-IgG might be non-neutralizing whereas RBD-IgGAM appears to be a good surrogate marker to estimate nAb levels. A third vaccination increases the nAb response. Furthermore, the systemic vaccine does not seem to elicit readily detectable mucosal immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0263861","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T13:38:41Z","timestamp":1666100321000},"page":"e0263861","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Evaluation of the systemic and mucosal immune response induced by COVID-19 and the BNT162b2 mRNA vaccine for SARS-CoV-2"],"prefix":"10.1371","volume":"17","author":[{"given":"Olaf","family":"Nickel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rockstroh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"Landgraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Kalbitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Kellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6029-3368","authenticated-orcid":true,"given":"Corinna","family":"Pietsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Fertey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"L\u00fcbbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ulbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-7836","authenticated-orcid":true,"given":"Stephan","family":"Borte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"issue":"19","key":"pone.0263861.ref001","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months","volume":"385","author":"SJ Thomas","year":"2021","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0263861.ref002","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1038\/s41467-020-18450-4","article-title":"A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity","volume":"11","author":"AT Huang","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0263861.ref003","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1080\/22221751.2021.1913973","article-title":"Correlation of humoral immune responses to different SARS-CoV-2 antigens with virus neutralizing antibodies and symptomatic severity in a German COVID-19 cohort","volume":"10","author":"A Rockstroh","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"pone.0263861.ref004","article-title":"SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans","author":"JS Turner","year":"2020","journal-title":"Res Sq"},{"issue":"6529","key":"pone.0263861.ref005","article-title":"Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection","volume":"371","author":"JM Dan","year":"2021","journal-title":"Science"},{"issue":"5","key":"pone.0263861.ref006","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"LR Baden","year":"2021","journal-title":"N Engl J Med"},{"issue":"27","key":"pone.0263861.ref007","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"FP Polack","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0263861.ref008","unstructured":"Centers-for-Disease-Control-and-Prevention. SARS-CoV-2 Variant Classifications and Definitions 2021; Available from: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/variants\/variant-classifications.html."},{"issue":"24","key":"pone.0263861.ref009","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2021.26.24.2100509","article-title":"Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021","volume":"26","author":"F Campbell","year":"2021","journal-title":"Euro Surveill"},{"issue":"9","key":"pone.0263861.ref010","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/j.cell.2021.03.013","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"WF Garcia-Beltran","year":"2021","journal-title":"Cell"},{"issue":"4","key":"pone.0263861.ref011","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41591-021-01294-w","article-title":"Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies","volume":"27","author":"RE Chen","year":"2021","journal-title":"Nat Med"},{"issue":"7889","key":"pone.0263861.ref012","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41586-021-04085-y","article-title":"Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity","volume":"600","author":"C Lucas","year":"2021","journal-title":"Nature"},{"issue":"10271","key":"pone.0263861.ref013","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0140-6736(21)00144-6","article-title":"South Africa responds to new SARS-CoV-2 variant","volume":"397","author":"M. Makoni","year":"2021","journal-title":"Lancet"},{"issue":"7","key":"pone.0263861.ref014","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/s41591-021-01397-4","article-title":"SARS-CoV-2 variants of concern are emerging in India","volume":"27","author":"J Singh","year":"2021","journal-title":"Nat Med"},{"key":"pone.0263861.ref015","article-title":"The emergence and epidemic characteristics of the highly mutated SARS-CoV-2 Omicron variant","author":"D Tian","year":"2022","journal-title":"J Med Virol"},{"key":"pone.0263861.ref016","volume-title":"Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern: World Health Organisation","author":"World-Health-Organisation","year":"2021"},{"key":"pone.0263861.ref017","doi-asserted-by":"crossref","first-page":"32973","DOI":"10.1038\/srep32973","article-title":"Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs","volume":"6","author":"A Dutta","year":"2016","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0263861.ref018","doi-asserted-by":"crossref","first-page":"100230","DOI":"10.1016\/j.xcrm.2021.100230","article-title":"A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques","volume":"2","author":"AO Hassan","year":"2021","journal-title":"Cell Rep Med"},{"issue":"3","key":"pone.0263861.ref019","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/infdis\/jiab256","article-title":"Persisting Salivary IgG Against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys","volume":"224","author":"H Alkharaan","year":"2021","journal-title":"J Infect Dis"},{"key":"pone.0263861.ref020","unstructured":"BNT162b2 Fact sheet 2021 [18.08.2021]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/comirnaty-epar-product-information_en.pdf."},{"key":"pone.0263861.ref021","unstructured":"ChAdOx1-S Fact sheet: EMA; 2021 [18.08.2021]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/vaxzevria-previously-covid-19-vaccine-astrazeneca-epar-product-information_en.pdf."},{"issue":"8","key":"pone.0263861.ref022","doi-asserted-by":"crossref","first-page":"e192","DOI":"10.1016\/S1473-3099(20)30483-7","article-title":"A minimal common outcome measure set for COVID-19 clinical research","volume":"20","author":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"7868","key":"pone.0263861.ref023","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41586-021-03653-6","article-title":"BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans","volume":"595","author":"U Sahin","year":"2021","journal-title":"Nature"},{"key":"pone.0263861.ref024","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","author":"DS Khoury","year":"2021","journal-title":"Nat Med"},{"issue":"25","key":"pone.0263861.ref025","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1056\/NEJMoa2106599","article-title":"Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel","volume":"385","author":"T Pilishvili","year":"2021","journal-title":"N Engl J Med"},{"issue":"20","key":"pone.0263861.ref026","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1056\/NEJMoa2022483","article-title":"An mRNA Vaccine against SARS-CoV-2\u2014Preliminary Report","volume":"383","author":"LA Jackson","year":"2020","journal-title":"N Engl J Med"},{"issue":"7855","key":"pone.0263861.ref027","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","article-title":"mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants","volume":"592","author":"Z 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SARS-CoV-2 anti-spike antibodies more than double the half-life of anti-nucleocapsid antibodies in healthcare workers","author":"J Van Elslande","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"4","key":"pone.0263861.ref035","doi-asserted-by":"crossref","first-page":"115382","DOI":"10.1016\/j.diagmicrobio.2021.115382","article-title":"Comprehensive evaluation of eight commercial SARS-CoV-2 IgG assays","volume":"100","author":"M Honemann","year":"2021","journal-title":"Diagn Microbiol Infect Dis"},{"key":"pone.0263861.ref036","article-title":"The SARS-CoV-2 mRNA-1273 vaccine elicits more RBD-focused neutralization, but with broader antibody binding within the RBD","author":"AJ Greaney","year":"2021","journal-title":"bioRxiv"},{"issue":"24","key":"pone.0263861.ref037","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1056\/NEJMoa2114583","article-title":"Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months","volume":"385","author":"EG Levin","year":"2021","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0263861.ref038","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJMoa2115481","article-title":"Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines","volume":"386","author":"N Andrews","year":"2022","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0263861.ref039","first-page":"281","article-title":"Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6\u20138 months after the infection","volume":"2","author":"N Sherina","year":"2021","journal-title":"Med (N Y)"},{"issue":"7854","key":"pone.0263861.ref040","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41586-021-03402-9","article-title":"Detection of a SARS-CoV-2 variant of concern in South Africa","volume":"592","author":"H Tegally","year":"2021","journal-title":"Nature"},{"issue":"4","key":"pone.0263861.ref041","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus","volume":"182","author":"B Korber","year":"2020","journal-title":"Cell"},{"issue":"9","key":"pone.0263861.ref042","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1016\/j.cell.2021.02.037","article-title":"Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera","volume":"184","author":"D Zhou","year":"2021","journal-title":"Cell"},{"issue":"9","key":"pone.0263861.ref043","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1016\/j.cell.2021.03.036","article-title":"SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies","volume":"184","author":"M 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