{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:32:52Z","timestamp":1791999172037,"version":"4.4.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking \u22482 weeks and subsiding to background levels \u2248 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In &gt;90% of vaccinees, <jats:italic>in vitro<\/jats:italic> expandable T cells could still be detected &gt;10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.<\/jats:p>","DOI":"10.1038\/s41598-017-00798-1","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T08:15:48Z","timestamp":1490948148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination"],"prefix":"10.1038","volume":"7","author":[{"given":"Michael","family":"Kongsgaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Bassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Skj\u00f8dt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Thybo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Bagge","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-9479","authenticated-orcid":false,"given":"Jan Pravsgaard","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9803","authenticated-orcid":false,"given":"Allan Randrup","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren","family":"Buus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Stryhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,6]]},"reference":[{"key":"798_CR1","unstructured":"Monath, T. 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J Exp Med \n                           202, 1179\u20131184 (2005).","journal-title":"J Exp Med"},{"key":"798_CR20","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/icb.2010.155","volume":"89","author":"R Ahmed","year":"2011","unstructured":"Ahmed, R. & Akondy, R. S. Insights into human CD8(+) T-cell memory using the yellow fever and smallpox vaccines. Immunol Cell Biol \n                           89, 340\u2013345 (2011).","journal-title":"Immunol Cell Biol"},{"key":"798_CR21","doi-asserted-by":"publisher","first-page":"7919","DOI":"10.4049\/jimmunol.0803903","volume":"183","author":"RS Akondy","year":"2009","unstructured":"Akondy, R. S. et al. The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J Immunol \n                           183, 7919\u20137930 (2009).","journal-title":"J Immunol"},{"key":"798_CR22","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s10875-008-9267-3","volume":"29","author":"J Wrammert","year":"2009","unstructured":"Wrammert, J., Miller, J., Akondy, R. & Ahmed, R. Human immune memory to yellow fever and smallpox vaccination. J Clin Immunol \n                           29, 151\u2013157 (2009).","journal-title":"J Clin Immunol"},{"key":"798_CR23","doi-asserted-by":"publisher","first-page":"e718","DOI":"10.1111\/j.1365-2567.2009.03070.x","volume":"128","author":"MD Co","year":"2009","unstructured":"Co, M. D., Kilpatrick, E. D. & Rothman, A. L. Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization. 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J Infect Dis \n                           204, 873\u2013883 (2011).","journal-title":"J Infect Dis"},{"key":"798_CR26","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.immuni.2008.02.020","volume":"28","author":"JD Miller","year":"2008","unstructured":"Miller, J. D. et al. Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity \n                           28, 710\u2013722 (2008).","journal-title":"Immunity"},{"key":"798_CR27","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.4049\/jimmunol.1402605","volume":"194","author":"MR Bassi","year":"2015","unstructured":"Bassi, M. R. et al. CD8+ T cells complement antibodies in protecting against yellow fever virus. 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J Immunol \n                           190, 2150\u20132158 (2013).","journal-title":"J Immunol"},{"key":"798_CR30","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1016\/j.vaccine.2006.12.038","volume":"25","author":"M Wang","year":"2007","unstructured":"Wang, M. et al. CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening. Vaccine \n                           25, 2823\u20132831 (2007).","journal-title":"Vaccine"},{"issue":"Pt A","key":"798_CR31","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0091-679X(08)60603-2","volume":"43","author":"TC Becker","year":"1994","unstructured":"Becker, T. C. et al. Use of recombinant adenovirus for metabolic engineering of mammalian cells. 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Travel Med Infect Dis \n                           11, 266\u2013273 (2013).","journal-title":"Travel Med Infect Dis"},{"key":"798_CR41","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/(SICI)1096-9071(199810)56:2<159::AID-JMV10>3.0.CO;2-B","volume":"56","author":"B Reinhardt","year":"1998","unstructured":"Reinhardt, B., Jaspert, R., Niedrig, M., Kostner, C. & L\u2019Age-Stehr, J. Development of viremia and humoral and cellular parameters of immune activation after vaccination with yellow fever virus strain 17D: a model of human flavivirus infection. J Med Virol \n                           56, 159\u2013167 (1998).","journal-title":"J Med Virol"},{"key":"798_CR42","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1007\/s13149-011-0135-7","volume":"104","author":"H Coulange Bodilis","year":"2011","unstructured":"Coulange Bodilis, H. et al. Long term persistence of yellow fever neutralising antibodies in elderly persons. 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Proc Natl Acad Sci USA \n                           112, 3050\u20133055 (2015).","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00798-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00798-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00798-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:29:50Z","timestamp":1671766190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00798-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,6]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["798"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-00798-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,6]]},"assertion":[{"value":"1 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"662"}}