{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:07:13Z","timestamp":1772741233039,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>While mRNA vaccines are administrated worldwide in an effort to contain the COVID-19 pandemic, the heterogeneity of the humoral immune response they induce at the population scale remains unclear. Here, in a prospective, longitudinal, cohort-study, including 1245 hospital care workers and 146 nursing home residents scheduled for BNT162b2 vaccination, together covering adult ages from 19 to 99 years, we analyse seroconversion to SARS-CoV-2 spike protein and amount of spike-specific IgG, IgM and IgA before vaccination, and 3-5 weeks after each dose. We show that immunogenicity after a single vaccine dose is biased to IgG, heterogeneous and reduced with increasing age. The second vaccine dose normalizes IgG seroconversion in all age strata. These findings indicate two dose mRNA vaccines is required to reach population scale humoral immunity. The results advocate for the interval between the two doses not to be extended, and for serological monitoring of elderly and immunosuppressed vaccinees.<\/jats:p>","DOI":"10.1038\/s41467-021-27761-z","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T06:02:59Z","timestamp":1641794579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Population homogeneity for the antibody response to COVID-19 BNT162b2\/Comirnaty vaccine is only reached after the second dose across all adult age ranges"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-1221","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Faro-Viana","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0691-4308","authenticated-orcid":false,"given":"Marie-Louise","family":"Bergman","sequence":"additional","affiliation":[]},{"given":"L\u00edgia A.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-4492","authenticated-orcid":false,"given":"N\u00e1dia","family":"Duarte","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-0725","authenticated-orcid":false,"given":"Teresa P.","family":"Coutinho","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia C.","family":"Borges","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Diwo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-0649","authenticated-orcid":false,"given":"Rute","family":"Castro","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Matoso","sequence":"additional","affiliation":[]},{"given":"Vanessa","family":"Malheiro","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Brennand","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-0006","authenticated-orcid":false,"given":"Lindsay","family":"Kosack","sequence":"additional","affiliation":[]},{"given":"Onome","family":"Akpogheneta","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o M.","family":"Figueira","sequence":"additional","affiliation":[]},{"given":"Concei\u00e7\u00e3o","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Ana M.","family":"Casaca","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-3556","authenticated-orcid":false,"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-5366","authenticated-orcid":false,"given":"Telmo","family":"Nunes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7225-1907","authenticated-orcid":false,"given":"Carlos","family":"Penha-Gon\u00e7alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-614X","authenticated-orcid":false,"given":"Jocelyne","family":"Demengeot","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"27761_CR1","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"New Engl. J. Med."},{"key":"27761_CR2","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1056\/NEJMoa2027906","volume":"383","author":"EE Walsh","year":"2020","unstructured":"Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. New Engl. J. Med. 383, 2439\u20132450 (2020).","journal-title":"New Engl. J. Med."},{"key":"27761_CR3","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","volume":"584","author":"EJ Williamson","year":"2020","unstructured":"Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430\u2013436 (2020).","journal-title":"Nature"},{"key":"27761_CR4","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.smim.2018.10.010","volume":"40","author":"A Ciabattini","year":"2018","unstructured":"Ciabattini, A. et al. Vaccination in the elderly: the challenge of immune changes with aging. Semin. Immunol. 40, 83\u201394 (2018).","journal-title":"Semin. Immunol."},{"key":"27761_CR5","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","volume":"16","author":"SL Klein","year":"2016","unstructured":"Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626\u2013638 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"27761_CR6","doi-asserted-by":"crossref","unstructured":"Wang, Z. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616\u2013622 (2021).","DOI":"10.1038\/s41586-021-03324-6"},{"key":"27761_CR7","doi-asserted-by":"crossref","unstructured":"Manisty, C. et al. Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals. Lancet 397, 1057\u20131058 (2021).","DOI":"10.1016\/S0140-6736(21)00501-8"},{"key":"27761_CR8","doi-asserted-by":"crossref","unstructured":"Krammer, F. et al. Antibody responses in seropositive persons after a single dose of SARS-CoV-2 mRNA vaccine. New Engl. J. Med. 384, 1372\u20131374 (2021).","DOI":"10.1056\/NEJMc2101667"},{"key":"27761_CR9","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1056\/NEJMc2103916","volume":"384","author":"N Doria-Rose","year":"2021","unstructured":"Doria-Rose, N. et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. New Engl. J. Med. 384, 2259\u20132261 (2021).","journal-title":"New Engl. J. 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Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6-8 months after the infection. Med 2, 281\u2013295 e284 (2021).","journal-title":"Med"},{"key":"27761_CR19","doi-asserted-by":"crossref","unstructured":"Sterlin, D. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci. Transl. Med. 13, eabd2223 (2021).","DOI":"10.1126\/scitranslmed.abd2223"},{"key":"27761_CR20","doi-asserted-by":"crossref","unstructured":"Wang, Z. et al. Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci. Transl. Med. 13, eabf1555 (2021).","DOI":"10.1126\/scitranslmed.abf1555"},{"key":"27761_CR21","doi-asserted-by":"publisher","unstructured":"Mades, A. et al. 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Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet 397, 1819\u20131829 (2021).","journal-title":"Lancet"},{"key":"27761_CR30","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41591-020-0913-5","volume":"26","author":"F Amanat","year":"2020","unstructured":"Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. 26, 1033\u20131036 (2020).","journal-title":"Nat. Med."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-27761-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-27761-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-27761-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T10:32:41Z","timestamp":1669285961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-27761-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,10]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["27761"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-27761-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.19.21253680","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,10]]},"assertion":[{"value":"5 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"140"}}