{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:02:24Z","timestamp":1775761344626,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vaccines are a cornerstone of global public health, but their efficacy can vary significantly among individuals. Bacille Calmette\u2010Gu\u00e9rin (BCG) vaccine against tuberculosis is one of the most used vaccines, and its efficacy is influenced by numerous factors, including sex, age, and geographical location. Systematic investigations using large\u2010scale multi\u2010omics analyses to dissect sex\u2010specific determinants of vaccine efficacy remain limited. To better understand this variability and improve vaccine efficacy, we analyzed multi\u2010omics data from a cohort of 321 healthy individuals vaccinated with BCG, integrating immune cell frequencies, single\u2010cell RNA sequencing, plasma proteins, metabolites, and DNA methylation profiles. Our findings revealed significant sex\u2010specific differences in immune pathways that contribute to BCG efficacy. In males, pre\u2010vaccination signatures were associated with a stronger pro\u2010inflammatory response, highlighting the importance of an innate\u2010driven immune response, while females exhibited enhanced antigen presentation pathways and adaptive immune responses. This study underscores the need for understanding individual baseline immune status in relation to biological sex, an approach that could represent a promising path to optimizing vaccine effectiveness.<\/jats:p>","DOI":"10.1002\/eji.70144","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:02:13Z","timestamp":1770901333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Analysis Reveals Sex\u2010Specific Signatures for BCG Vaccine Efficacy"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7928-9300","authenticated-orcid":false,"given":"Qiuyao","family":"Zhan","sequence":"first","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianbo","family":"Fu","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone J.C.F.M.","family":"Moorlag","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie A.C.M.","family":"Koeken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Charlotte J.","family":"de Bree","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera P.","family":"Mourits","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo A.B.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department of Medical Genetics Iuliu Hatieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Community For Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department For Immunology and Metabolism Life and Medical Sciences Institute (LIMES). University of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Centre For Individualised Infection Medicine (CiiM) a Joint Venture Between the Helmholtz Centre For Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"},{"name":"TWINCORE a Joint Venture Between the Helmholtz\u2010Centre for Infection Research (HZI) and Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(06)68507\u20103"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.11.004"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2249"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/314072"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","unstructured":"C.Qi Z.Liu G.Kilic et\u00a0al.Epigenetic Reprogramming Mediates Monocyte and Heterologous T Cell\u2010Derived Cytokine Responses After BCG Vaccination. Preprint posted online March 28 2024 https:\/\/doi.org\/10.1101\/2024.03.27.24304976.","DOI":"10.1101\/2024.03.27.24304976"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133935"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001765"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010021\u201002482\u20100"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112487"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035088\u20106"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010018\u20100121\u20103"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(18)30052\u20103"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix612"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.09.006"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000231546.14749.ab"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.03.038"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.09.039"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600781R"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6098"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321060111"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.04.001"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.12.005"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.49"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b21\u201000574"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2008.5"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001329\u20105"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874312901206010209"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20178124"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2016.04.012"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384\u2010020\u201003582\u20102"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.01.031"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001406"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MA0118\u2010027R"},{"key":"e_1_2_13_36_1","doi-asserted-by":"crossref","unstructured":"A. N.Pelletier G.Sanchez M.Watson et\u00a0al. \u201cA Prevaccination Validated Network That Drives the Breadth of the Protective Neutralizing Antibody Response Following Dengue Vaccine TV003 Immunization \u201d Preprint posted online September 28 2021 https:\/\/doi.org\/10.1101\/2021.09.25.21264123.","DOI":"10.1101\/2021.09.25.21264123"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23417"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00860"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0287128"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541\u2010024\u201001022\u20108"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010022\u201000763\u20104"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.038"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1928"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.017"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1630"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac201267k"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1089"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1037"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095192"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1156"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.70144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.70144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:11:39Z","timestamp":1775758299000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/eji.70144"],"URL":"https:\/\/doi.org\/10.1002\/eji.70144","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70144"}}