{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:36:41Z","timestamp":1790487401611,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T00:00:00Z","timestamp":1549324800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF108"],"award-info":[{"award-number":["DNRF108"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["#310372"],"award-info":[{"award-number":["#310372"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001722","name":"Koninklijke Nederlandse Akademie van Wetenschappen","doi-asserted-by":"publisher","award":["Spinoza Grant"],"award-info":[{"award-number":["Spinoza Grant"]}],"id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Microbiol Infect Dis"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1007\/s10096-018-03449-z","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T03:50:02Z","timestamp":1549338602000},"page":"449-456","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Opposite effects of Vaccinia and modified Vaccinia Ankara on trained immunity"],"prefix":"10.1007","volume":"38","author":[{"given":"Bastiaan A.","family":"Blok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer J.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Aaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Fomsgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinout","family":"van Crevel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S.","family":"Benn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,5]]},"reference":[{"issue":"2","key":"3449_CR1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1093\/cid\/cit209","volume":"57","author":"KL Flanagan","year":"2013","unstructured":"Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O (2013) Heterologous (\u2018non-specific\u2019) and sex-differential effects of vaccines: epidemiology, clinical trials and emerging immunological mechanisms. Clin Infect Dis 57(2):283\u2013289","journal-title":"Clin Infect Dis"},{"issue":"2","key":"3449_CR2","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1093\/infdis\/jir240","volume":"204","author":"P Aaby","year":"2011","unstructured":"Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM et al (2011) Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis 204(2):245\u2013252 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21673035 . [cited 2012 Nov 21]","journal-title":"J Infect Dis"},{"issue":"11","key":"3449_CR3","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1093\/infdis\/jit804","volume":"209","author":"CL Martins","year":"2014","unstructured":"Martins CL, Benn CS, Andersen A, Bal\u00e9 C, Schaltz-Buchholzer F, Do VA et al (2014) A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions. J Infect Dis 209(11):1731\u20131738","journal-title":"J Infect Dis"},{"issue":"6","key":"3449_CR4","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nri.2016.43","volume":"16","author":"HS Goodridge","year":"2016","unstructured":"Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O, Netea MG et al (2016) Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol 16(6):392\u2013400 Available from: http:\/\/www.nature.com\/nri\/journal\/vaop\/ncurrent\/full\/nri.2016.43.html?WT.mc_id=FBK_NatureReviews","journal-title":"Nat Rev Immunol"},{"issue":"nov30 2","key":"3449_CR5","doi-asserted-by":"publisher","first-page":"c6495","DOI":"10.1136\/bmj.c6495","volume":"341","author":"P Aaby","year":"2010","unstructured":"Aaby P, Martins CL, Garly M-L, Bale C, Andersen A, Rodrigues A et al (2010) Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ 341(nov30 2):c6495\u2013c6495 Available from: http:\/\/www.bmj.com\/cgi\/doi\/10.1136\/bmj.c6495 . [cited 2012 Nov 24]","journal-title":"BMJ"},{"issue":"10","key":"3449_CR6","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1093\/cid\/civ617","volume":"61","author":"N Lund","year":"2015","unstructured":"Lund N, Andersen A, Hansen ASK, Jepsen FS, Barbosa A, Biering-S\u00f8rensen S et al (2015) The effect of oral polio vaccine at birth on infant mortality: a randomized trial. Clin Infect Dis 61(10):1504\u20131511","journal-title":"Clin Infect Dis"},{"issue":"1","key":"3449_CR7","doi-asserted-by":"publisher","first-page":"e101","DOI":"10.1371\/journal.pone.0000101","volume":"1","author":"ML Jensen","year":"2006","unstructured":"Jensen ML, Dave S, Schim van der Loeff M, da Costa C, Vincent T, Leligdowicz A et al (2006) Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau. PLoS One 1(1):e101 Available from: http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?artid=1762358&tool=pmcentrez&rendertype=abstract . [cited 2014 Jun 16]","journal-title":"PLoS One"},{"issue":"29\u201330","key":"3449_CR8","doi-asserted-by":"publisher","first-page":"5718","DOI":"10.1016\/j.vaccine.2006.04.045","volume":"24","author":"P Aaby","year":"2006","unstructured":"Aaby P, Gustafson P, Roth A, Rodrigues A, Fernandes M, Sodemann M et al (2006) Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau. Vaccine 24(29\u201330):5718\u20135725 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16720061 . [cited 2014 Jun 16]","journal-title":"Vaccine"},{"key":"3449_CR9","first-page":"1","volume":"94","author":"A Rieckmann","year":"2016","unstructured":"Rieckmann A, Villumsen M, S\u00f8rup S, Haugaard LK, Ravn H, Roth A et al (2016) Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971\u20132010. Int J Epidemiol 94:1\u201311","journal-title":"Int J Epidemiol"},{"issue":"5","key":"3449_CR10","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s10552-008-9259-x","volume":"20","author":"HA Lankes","year":"2009","unstructured":"Lankes HA, Fought AJ, Evens AM, Weisenburger DD, Chiu BC-H (2009) Vaccination history and risk of non-Hodgkin lymphoma: a population-based, case-control study. Cancer Causes Control 20(5):517\u2013523 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19011978 . [cited 2016 Jun 24]","journal-title":"Cancer Causes Control"},{"issue":"3","key":"3449_CR11","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1046\/j.1523-1747.2002.00643.x","volume":"119","author":"A Pfahlberg","year":"2002","unstructured":"Pfahlberg A, K\u00f6lmel KF, Grange JM, Mastrangelo G, Krone B, Botev IN et al (2002) Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study. J Invest Dermatol 119(3):570\u2013575 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12230497 . [cited 2016 Aug 19]","journal-title":"J Invest Dermatol"},{"issue":"43","key":"3449_CR12","doi-asserted-by":"publisher","first-page":"17537","DOI":"10.1073\/pnas.1202870109","volume":"109","author":"J Kleinnijenhuis","year":"2012","unstructured":"Kleinnijenhuis J, Quintin J, Preijers F, AB JL, Ifrim DC, Saeed S et al (2012) Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 109(43):17537\u201317542 Available from: http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?artid=3491454&tool=pmcentrez&rendertype=abstract . [cited 2012 Nov 21]","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"3449_CR13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1189\/jlb.5RI0315-096R","volume":"98","author":"BA Blok","year":"2015","unstructured":"Blok BA, Arts RJW, van Crevel R, Benn CS, Netea MG (2015) Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines. J Leukoc Biol 98(3):347\u2013356 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26150551","journal-title":"J Leukoc Biol"},{"issue":"12","key":"3449_CR14","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1086\/421266","volume":"38","author":"LH McCurdy","year":"2004","unstructured":"McCurdy LH, Larkin BD, Martin JE, Graham BS (2004) Modified Vaccinia Ankara: potential as an alternative smallpox vaccine. Clin Infect Dis 38(12):1749\u20131753 Available from: http:\/\/cid.oxfordjournals.org\/lookup\/doi\/10.1086\/421266 . [cited 2016 Jun 24]","journal-title":"Clin Infect Dis"},{"issue":"5","key":"3449_CR15","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S0147-9571(03)00025-0","volume":"26","author":"A Mayr","year":"2003","unstructured":"Mayr A (2003) Smallpox vaccination and bioterrorism with pox viruses. Comp Immunol Microbiol Infect Dis 26(5):423\u2013430","journal-title":"Comp Immunol Microbiol Infect Dis"},{"issue":"9871","key":"3449_CR16","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0140-6736(13)60177-4","volume":"381","author":"MD Tameris","year":"2013","unstructured":"Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S et al (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381(9871):1021\u20131028. https:\/\/doi.org\/10.1016\/S0140-6736(13)60177-4 [cited 2014 May 27]","journal-title":"Lancet"},{"issue":"3","key":"3449_CR17","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/S2213-2600(15)00037-5","volume":"3","author":"BP Ndiaye","year":"2015","unstructured":"Ndiaye BP, Thienemann F, Ota M, Landry BS, Camara M, Di\u00e8ye S et al (2015) Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial. Lancet Respir Med 3(3):190\u2013200 Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213260015000375 . [cited 2016 Jun 24]","journal-title":"Lancet Respir Med"},{"issue":"1\u20132","key":"3449_CR18","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0022-1759(03)00231-X","volume":"278","author":"U Repnik","year":"2003","unstructured":"Repnik U, Knezevic M, Jeras M (2003) Simple and cost-effective isolation of monocytes from buffy coats. J Immunol Methods 278(1\u20132):283\u2013292","journal-title":"J Immunol Methods"},{"issue":"2","key":"3449_CR19","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.chom.2012.06.006","volume":"12","author":"J Quintin","year":"2012","unstructured":"Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C et al (2012) Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12(2):223\u2013232","journal-title":"Cell Host Microbe"},{"issue":"5","key":"3449_CR20","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.4049\/jimmunol.129.5.2239","volume":"129","author":"H Yang","year":"1982","unstructured":"Yang H, Cain CA, Woan MC, Tompkins WA (1982) Evaluation of hamster natural cytotoxic cells and vaccinia-induced cytotoxic cells for Thy-1.2 homologue by using a mouse monoclonal alpha-Thy-1.2 antibody. J Immunol (Baltimore, Md 1950) 129(5):2239\u20132243","journal-title":"J Immunol (Baltimore, Md 1950)"},{"key":"3449_CR21","first-page":"2652","volume":"152","author":"EA Carpenter","year":"1994","unstructured":"Carpenter EA, Ruby J, Ramshaw IA (1994) IFN-y, TNF, and IL-6 production by vaccinia virus immune spleen cells. An In Vitro Study J Immunol 152:2652\u20132659","journal-title":"An In Vitro Study J Immunol"},{"issue":"3","key":"3449_CR22","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1128\/IAI.21.3.886-895.1978","volume":"21","author":"CJ Schleupner","year":"1978","unstructured":"Schleupner CJ, Glasgow LA (1978) Peritoneal macrophage activation indicated by enhanced chemiluminescence. Infect Immun 21(3):886\u2013895","journal-title":"Infect Immun"},{"issue":"20","key":"3449_CR23","doi-asserted-by":"publisher","first-page":"9977","DOI":"10.1128\/JVI.00354-06","volume":"80","author":"L Deng","year":"2006","unstructured":"Deng L, Dai P, Ding W, Granstein RD, Shuman S (2006) Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells. J Virol 80(20):9977\u20139987","journal-title":"J Virol"},{"issue":"1","key":"3449_CR24","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jpeds.2015.03.035","volume":"167","author":"K Nohmi","year":"2015","unstructured":"Nohmi K, Tokuhara D, Tachibana D, Saito M, Sakashita Y, Nakano A et al (2015) Zymosan induces immune responses comparable with those of adults in monocytes, dendritic cells, and monocyte-derived dendritic cells from cord blood. J Pediatr 167(1):155\u2013162.e2. https:\/\/doi.org\/10.1016\/j.jpeds.2015.03.035","journal-title":"J Pediatr"},{"key":"3449_CR25","doi-asserted-by":"crossref","unstructured":"Bekkering S, Blok BA, Joosten LA, Riksen NP, van Crevel R, Netea MG (2016) In vitro experimental model of trained innate immunity in human primary monocytes. Clin Vaccine Immunol. 23(12):926\u2013933","DOI":"10.1128\/CVI.00349-16"},{"issue":"35","key":"3449_CR26","doi-asserted-by":"publisher","first-page":"6458","DOI":"10.1016\/j.vaccine.2007.06.035","volume":"25","author":"CA Scherer","year":"2007","unstructured":"Scherer CA, Magness CL, Steiger KV, Poitinger ND, Caputo CM, Miner DG et al (2007) Distinct gene expression profiles in peripheral blood mononuclear cells from patients infected with vaccinia virus, yellow fever 17D virus, or upper respiratory infections. Vaccine 25(35):6458\u20136473","journal-title":"Vaccine"},{"issue":"39","key":"3449_CR27","doi-asserted-by":"publisher","first-page":"4231","DOI":"10.1016\/j.vaccine.2013.03.017","volume":"31","author":"PJR Price","year":"2013","unstructured":"Price PJR, Torres-Dom\u00ednguez LE, Brandm\u00fcller C, Sutter G, Lehmann MH (2013) Modified vaccinia virus Ankara: innate immune activation and induction of cellular signalling. Vaccine 31(39):4231\u20134234. https:\/\/doi.org\/10.1016\/j.vaccine.2013.03.017 [cited 2014 Jun 16]","journal-title":"Vaccine"},{"issue":"8","key":"3449_CR28","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1002\/eji.201343403","volume":"43","author":"A Y\u00e1\u00f1ez","year":"2013","unstructured":"Y\u00e1\u00f1ez A, Hassanzadeh-Kiabi N, Ng MY, Meg\u00edas J, Subramanian A, Liu GY et al (2013) Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce. Eur J Immunol 43(8):2114\u20132125","journal-title":"Eur J Immunol"},{"issue":"4","key":"3449_CR29","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1111\/imm.12223","volume":"141","author":"AJ Verrall","year":"2014","unstructured":"Verrall AJ, Netea MG, Alisjahbana B, Hill PC, van Crevel R (2014) Early clearance of Mycobacterium tuberculosis: a new frontier in prevention. Immunology 141(4):506\u2013513 Available from: http:\/\/doi.wiley.com\/10.1111\/imm.12223 . [cited 2016 Jun 27]","journal-title":"Immunology"},{"issue":"6","key":"3449_CR30","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.smim.2014.09.006","volume":"26","author":"MG Netea","year":"2014","unstructured":"Netea MG, van Crevel R (2014) BCG-induced protection: effects on innate immune memory. Semin Immunol 26(6):512\u2013517 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25444548 . [cited 2016 Jun 24]","journal-title":"Semin Immunol"},{"issue":"1","key":"3449_CR31","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1006\/viro.2001.1090","volume":"288","author":"KL Oie","year":"2001","unstructured":"Oie KL, Pickup DJ (2001) Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-\u03baB activation. Virology 288(1):175\u2013187 Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0042682201910906 . [cited 2016 Jun 17]","journal-title":"Virology"},{"issue":"9","key":"3449_CR32","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1172\/JCI3877","volume":"102","author":"J Bohuslav","year":"1998","unstructured":"Bohuslav J, Kravchenko VV, Parry GC, Erlich JH, Gerondakis S, Mackman N et al (1998) Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. J Clin Invest 102(9):1645\u20131652 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9802878 . [cited 2016 Jun 17]","journal-title":"J Clin Invest"},{"issue":"4","key":"3449_CR33","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1128\/IAI.67.4.1553-1559.1999","volume":"67","author":"S Kasteenbauer","year":"1999","unstructured":"Kasteenbauer S, Ziegler-Heitbrock HW (1999) NF-kappaB1 (p50) is upregulated in lipopolysaccharide tolerance and can block tumor necrosis factor gene expression. Infect Immun 67(4):1553\u20131559 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10084986 . [cited 2016 Jun 17]","journal-title":"Infect Immun"},{"issue":"5","key":"3449_CR34","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.cell.2007.07.009","volume":"130","author":"FR Greten","year":"2007","unstructured":"Greten FR, Arkan MC, Bollrath J, Hsu L-C, Goode J, Miething C et al (2007) NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell 130(5):918\u2013931 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17803913 . [cited 2016 Jun 17]","journal-title":"Cell"}],"container-title":["European Journal of Clinical Microbiology & Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10096-018-03449-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-018-03449-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-018-03449-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T11:34:00Z","timestamp":1694604840000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10096-018-03449-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,5]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["3449"],"URL":"https:\/\/doi.org\/10.1007\/s10096-018-03449-z","relation":{},"ISSN":["0934-9723","1435-4373"],"issn-type":[{"value":"0934-9723","type":"print"},{"value":"1435-4373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,5]]},"assertion":[{"value":"12 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}