{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:29:10Z","timestamp":1793197750359,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100009318","name":"Helmholtz Association","doi-asserted-by":"publisher","award":["CoViPa consortium"],"award-info":[{"award-number":["CoViPa consortium"]}],"id":[{"id":"10.13039\/501100009318","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR179"],"award-info":[{"award-number":["TRR179"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bavarian State Ministry of Science, FOR-Covid consortium and CoVaKo study"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1038\/s41591-022-01715-4","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T09:09:39Z","timestamp":1643360979000},"page":"496-503","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":270,"title":["Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern"],"prefix":"10.1038","volume":"28","author":[{"given":"Paul R.","family":"Wratil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-6905","authenticated-orcid":false,"given":"Marcel","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4982-0347","authenticated-orcid":false,"given":"Alina","family":"Priller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Willmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Almanzar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6560-0136","authenticated-orcid":false,"given":"Emanuel","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-6503","authenticated-orcid":false,"given":"Martin","family":"Feuerherd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho-Chin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Yazici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Christa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Jeske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2786-6627","authenticated-orcid":false,"given":"Gaia","family":"Lupoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Vogt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-7599","authenticated-orcid":false,"given":"Manuel","family":"Albanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-8177","authenticated-orcid":false,"given":"Ernesto","family":"Mej\u00edas-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-5032","authenticated-orcid":false,"given":"Stefan","family":"Bauernfried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Mijocevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Vu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Tinnefeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Wettengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-0470","authenticated-orcid":false,"given":"Maximilian","family":"Muenchhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-3099","authenticated-orcid":false,"given":"Christopher","family":"Daechert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Mairhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Fingerle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Steininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-2332","authenticated-orcid":false,"given":"Helmut","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-194X","authenticated-orcid":false,"given":"Veit","family":"Hornung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Liebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"\u00dcberla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Prelog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2983-0414","authenticated-orcid":false,"given":"Percy","family":"Knolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-8946","authenticated-orcid":false,"given":"Oliver T.","family":"Keppler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1911","authenticated-orcid":false,"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"1715_CR1","doi-asserted-by":"publisher","unstructured":"Mohapatra, R. K. et al. Omicron (B.1.1.529 variant of SARS-CoV-2); an emerging threat: current global scenario. J. Med. Virol. https:\/\/doi.org\/10.1002\/jmv.27561 (2021).","DOI":"10.1002\/jmv.27561"},{"key":"1715_CR2","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41586-021-03470-x","volume":"593","author":"E Volz","year":"2021","unstructured":"Volz, E. et al. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature 593, 266\u2013269 (2021).","journal-title":"Nature"},{"key":"1715_CR3","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41586-021-03402-9","volume":"592","author":"H Tegally","year":"2021","unstructured":"Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438\u2013443 (2021).","journal-title":"Nature"},{"key":"1715_CR4","doi-asserted-by":"crossref","unstructured":"Fujino, T. et al. Novel SARS-CoV-2 variant in travelers from Brazil to Japan. Emerg. Infect. Dis. 27, 1243\u20131245 (2021).","DOI":"10.3201\/eid2704.210138"},{"key":"1715_CR5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41586-021-03944-y","volume":"599","author":"P Mlcochova","year":"2021","unstructured":"Mlcochova, P. et al. SARS-CoV-2 B.1.617.2 delta variant replication and immune evasion. Nature 599, 114\u2013119 (2021).","journal-title":"Nature"},{"key":"1715_CR6","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","volume":"592","author":"Z Wang","year":"2021","unstructured":"Wang, Z. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616\u2013622 (2021).","journal-title":"Nature"},{"key":"1715_CR7","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","volume":"596","author":"D Planas","year":"2021","unstructured":"Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276\u2013280 (2021).","journal-title":"Nature"},{"key":"1715_CR8","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1016\/S0140-6736(21)02758-6","volume":"398","author":"SSA Karim","year":"2021","unstructured":"Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet 398, 2126\u20132128 (2021).","journal-title":"Lancet"},{"key":"1715_CR9","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/s41586-021-04005-0","volume":"600","author":"F Schmidt","year":"2021","unstructured":"Schmidt, F. et al. High genetic barrier to SARS-CoV-2 polyclonal neutralizing antibody escape. Nature 600, 512\u2013516 (2021).","journal-title":"Nature"},{"key":"1715_CR10","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","volume":"27","author":"DS Khoury","year":"2021","unstructured":"Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205\u20131211 (2021).","journal-title":"Nat. Med."},{"key":"1715_CR11","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/j.immuni.2021.07.008","volume":"54","author":"F Muecksch","year":"2021","unstructured":"Muecksch, F. et al. Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth and resilience to viral escape mutations. Immunity 54, 1853\u20131868 (2021).","journal-title":"Immunity"},{"key":"1715_CR12","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1146\/annurev-immunol-020711-075032","volume":"30","author":"GD Victora","year":"2012","unstructured":"Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu. Rev. Immunol. 30, 429\u2013457 (2012).","journal-title":"Annu. Rev. Immunol."},{"key":"1715_CR13","doi-asserted-by":"publisher","first-page":"e240","DOI":"10.1016\/S2666-5247(21)00025-2","volume":"2","author":"WN Chia","year":"2021","unstructured":"Chia, W. N. et al. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. Lancet Microbe 2, e240\u2013e249 (2021).","journal-title":"Lancet Microbe"},{"key":"1715_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27649-y","volume":"13","author":"N Koerber","year":"2022","unstructured":"Koerber, N. et al. Dynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents. Nat. Commun. 13, 153 (2022).","journal-title":"Nat. Commun."},{"key":"1715_CR15","doi-asserted-by":"publisher","first-page":"e3055","DOI":"10.1093\/cid\/ciaa1935","volume":"73","author":"T Weinberger","year":"2021","unstructured":"Weinberger, T. et al. Prospective longitudinal serosurvey of healthcare workers in the first wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in a quaternary-care hospital in Munich, Germany. Clin. Infect. Dis. 73, e3055\u2013e3065 (2021).","journal-title":"Clin. Infect. Dis."},{"key":"1715_CR16","doi-asserted-by":"publisher","first-page":"2002066","DOI":"10.2807\/1560-7917.ES.2021.26.43.2002066","volume":"26","author":"M Muenchhoff","year":"2021","unstructured":"Muenchhoff, M. et al. Genomic epidemiology reveals multiple introductions of SARS-CoV-2 followed by community and nosocomial spread, Germany, February to May 2020. Euro Surveill. 26, 2002066 (2021).","journal-title":"Euro Surveill."},{"key":"1715_CR17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41586-021-03207-w","volume":"591","author":"C Gaebler","year":"2021","unstructured":"Gaebler, C. et al. Evolution of antibody immunity to SARS-CoV-2. Nature 591, 639\u2013644 (2021).","journal-title":"Nature"},{"key":"1715_CR18","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1016\/j.immuni.2021.06.015","volume":"54","author":"S Moriyama","year":"2021","unstructured":"Moriyama, S. et al. Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants. Immunity 54, 1841\u20131852 (2021).","journal-title":"Immunity"},{"key":"1715_CR19","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.cell.2021.01.050","volume":"184","author":"A Sokal","year":"2021","unstructured":"Sokal, A. et al. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response. Cell 184, 1201\u20131213 e1214 (2021).","journal-title":"Cell"},{"key":"1715_CR20","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1056\/NEJMc2119270","volume":"386","author":"S Collie","year":"2021","unstructured":"Collie, S., Champion, J., Moultrie, H., Bekker, L. G. & Gray, G. Effectiveness of BNT162b2 vaccine against Omicron variant in South Africa. N. Engl. J. Med. 386, 494\u2013496 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1715_CR21","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1056\/NEJMc2119358","volume":"386","author":"I Nemet","year":"2021","unstructured":"Nemet, I. et al. Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection. N. Engl. J. Med. 386, 492\u2013494 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1715_CR22","doi-asserted-by":"publisher","unstructured":"Garcia-Beltran, W. F. et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell https:\/\/doi.org\/10.1016\/j.cell.2021.12.033 (2022).","DOI":"10.1016\/j.cell.2021.12.033"},{"key":"1715_CR23","doi-asserted-by":"publisher","unstructured":"Carre\u00f1o, J. M. et al. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature https:\/\/doi.org\/10.1038\/s41586-022-04399-5 (2021).","DOI":"10.1038\/s41586-022-04399-5"},{"key":"1715_CR24","doi-asserted-by":"publisher","unstructured":"Gruell, H. et al. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat. Med. https:\/\/doi.org\/10.1038\/s41591-021-01676-0 (2022).","DOI":"10.1038\/s41591-021-01676-0"},{"key":"1715_CR25","doi-asserted-by":"publisher","unstructured":"Dejnirattisai, W. et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell https:\/\/doi.org\/10.1016\/j.cell.2021.12.046 (2022).","DOI":"10.1016\/j.cell.2021.12.046"},{"key":"1715_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1056\/NEJMoa2116298","volume":"386","author":"EB Walter","year":"2022","unstructured":"Walter, E. B. et al. Evaluation of the BNT162b2 COVID-19 vaccine in children 5 to 11 years of age. N. Engl. J. Med. 386, 35\u201346 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1715_CR27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","volume":"184","author":"A Sette","year":"2021","unstructured":"Sette, A. & Crotty, S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 184, 861\u2013880 (2021).","journal-title":"Cell"},{"key":"1715_CR28","doi-asserted-by":"publisher","first-page":"572","DOI":"10.3201\/eid2803.204436","volume":"28","author":"J Erber","year":"2022","unstructured":"Erber, J. et al. Infection control measures and prevalence of SARS-CoV-2 IgG among 4554 university hospital employees Munich Germany. Emerg. Infect. Dis. 28, 572\u2013581 (2022).","journal-title":"Emerg. Infect. Dis."},{"key":"1715_CR29","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1001\/jama.2021.3341","volume":"325","author":"S Saadat","year":"2021","unstructured":"Saadat, S. et al. Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2. JAMA 325, 1467\u20131469 (2021).","journal-title":"JAMA"},{"key":"1715_CR30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jim.2012.09.008","volume":"387","author":"G Almanzar","year":"2013","unstructured":"Almanzar, G., Ottensmeier, B., Liese, J. & Prelog, M. Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay using ammonium thiocyanate. J. Immunol. Methods 387, 36\u201342 (2013).","journal-title":"J. Immunol. Methods"},{"key":"1715_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-4-33","volume":"4","author":"RH Kneitz","year":"2004","unstructured":"Kneitz, R. H. et al. A new method for determination of varicella-zoster virus immunoglobulin G avidity in serum and cerebrospinal fluid. BMC Infect. Dis. 4, 33 (2004).","journal-title":"BMC Infect. Dis."},{"key":"1715_CR32","doi-asserted-by":"publisher","first-page":"2001057","DOI":"10.2807\/1560-7917.ES.2020.25.24.2001057","volume":"25","author":"M Muenchhoff","year":"2020","unstructured":"Muenchhoff, M. et al. Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020. Euro Surveill. 25, 2001057 (2020).","journal-title":"Euro Surveill."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01715-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01715-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01715-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T12:28:37Z","timestamp":1647865717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01715-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["1715"],"URL":"https:\/\/doi.org\/10.1038\/s41591-022-01715-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1226339\/v1","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]},"assertion":[{"value":"3 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests concerning the study content. Outside the study, they declare the following competing interests: U.P. is a cofounder, shareholder and board member of SCG Cell Therapy, a member of the scientific advisory board of Leukocare and a member of topic-specific scientific advisory boards of Sanofi-Pasteur, GILEAD and GSK and an ad hoc advisor for BioNTech (without remuneration).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}