{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:49:33Z","timestamp":1791823773981,"version":"4.3.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":110,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["495054088"],"award-info":[{"award-number":["495054088"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC UK","award":["MR\/W001217\/1"],"award-info":[{"award-number":["MR\/W001217\/1"]}]},{"DOI":"10.13039\/100016580","name":"Kennedy Trust for Rheumatology Research","doi-asserted-by":"publisher","award":["KENN212202"],"award-info":[{"award-number":["KENN212202"]}],"id":[{"id":"10.13039\/100016580","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y004450\/1"],"award-info":[{"award-number":["MR\/Y004450\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_PC_16056"],"award-info":[{"award-number":["MC_PC_16056"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["VaxHub Global"],"award-info":[{"award-number":["VaxHub Global"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","award":["2020-217289"],"award-info":[{"award-number":["2020-217289"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    BCG vaccination against TB may also reduce malaria incidence through non-specific innate immune activation. We investigated whether giving BCG alongside an adenoviral-vectored malaria vaccine improves protection against malaria in mice. Co-immunisation broadened and strengthened the early innate cytokine responses, enabling strong CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-dependent protection. Our findings suggest co-immunisation with BCG and adenoviral vector as a promising strategy to combat both TB and malaria in double-endemic regions.\n                  <\/jats:p>","DOI":"10.1038\/s41541-026-01506-9","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:55:23Z","timestamp":1782273323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BCG enables protection against malaria through adjuvanting an adenovirus-vectored vaccine"],"prefix":"10.1038","volume":"11","author":[{"given":"S\u00f6ren","family":"Reinke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ulaszewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Sims","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Guyon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Truby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundra","family":"Raissar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena S.","family":"Bezbradica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joannah R.","family":"Fergusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Milicic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"1506_CR1","doi-asserted-by":"crossref","unstructured":"Jurczak, M. & Druszczynska, M. Beyond tuberculosis: the surprising immunological benefits of the Bacillus Calmette-Guerin (BCG) vaccine in infectious, auto-immune, and inflammatory diseases. Pathogens 14, 196 (2025).","DOI":"10.3390\/pathogens14020196"},{"key":"1506_CR2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41581-022-00633-5","volume":"19","author":"J Ochando","year":"2023","unstructured":"Ochando, J., Mulder, W. J. M., Madsen, J. C., Netea, M. G. & Duivenvoorden, R. Trained immunity - basic concepts and contributions to immunopathology. Nat. Rev. Nephrol. 19, 23\u201337 (2023).","journal-title":"Nat. Rev. Nephrol."},{"key":"1506_CR3","doi-asserted-by":"crossref","unstructured":"de Araujo, A., Mambelli, F., Sanches, R. O., Marinho, F. V. & Oliveira, S. C. Current understanding of Bacillus Calmette-Guerin-mediated trained immunity and its perspectives for controlling intracellular infections. Pathogens 12, 1386 (2023).","DOI":"10.3390\/pathogens12121386"},{"key":"1506_CR4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/259309a0","volume":"259","author":"IA Clark","year":"1976","unstructured":"Clark, I. A., Allison, A. C. & Cox, F. E. Protection of mice against Babesia and Plasmodium with BCG. Nature 259, 309\u2013311 (1976).","journal-title":"Nature"},{"key":"1506_CR5","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/S0264-410X(00)00257-7","volume":"19","author":"S Matsumoto","year":"2000","unstructured":"Matsumoto, S. et al. Mycobacterium bovis Bacillus calmette-guerin induces protective immunity against infection by Plasmodium yoelii at blood-stage depending on shifting immunity toward Th1 type and inducing protective IgG2a after the parasite infection. Vaccine 19, 779\u2013787 (2000).","journal-title":"Vaccine"},{"key":"1506_CR6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1128\/iai.33.1.199-211.1981","volume":"33","author":"JR Murphy","year":"1981","unstructured":"Murphy, J. R. Host defenses in murine malaria: nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation. Infect. Immun. 33, 199\u2013211 (1981).","journal-title":"Infect. Immun."},{"key":"1506_CR7","doi-asserted-by":"publisher","first-page":"e66115","DOI":"10.1371\/journal.pone.0066115","volume":"8","author":"M Parra","year":"2013","unstructured":"Parra, M. et al. Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination. PLoS ONE 8, e66115 (2013).","journal-title":"PLoS ONE"},{"key":"1506_CR8","doi-asserted-by":"crossref","unstructured":"Witschkowski, J. et al. BCG provides short-term protection from experimental cerebral malaria in mice. Vaccines 8, 745 (2020).","DOI":"10.3390\/vaccines8040745"},{"key":"1506_CR9","doi-asserted-by":"publisher","first-page":"e001862","DOI":"10.1136\/bmjgh-2019-001862","volume":"4","author":"ML Berendsen","year":"2019","unstructured":"Berendsen, M. L. et al. BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa. BMJ Glob. Health 4, e001862 (2019).","journal-title":"BMJ Glob. Health"},{"key":"1506_CR10","doi-asserted-by":"publisher","first-page":"e001873","DOI":"10.1136\/bmjgh-2019-001873","volume":"5","author":"KJ Jensen","year":"2020","unstructured":"Jensen, K. J. et al. Seasonal variation in the non-specific effects of BCG vaccination on neonatal mortality: three randomised controlled trials in Guinea-Bissau. BMJ Glob. Health 5, e001873 (2020).","journal-title":"BMJ Glob. Health"},{"key":"1506_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08659-3","volume":"10","author":"J Walk","year":"2019","unstructured":"Walk, J. et al. Outcomes of controlled human malaria infection after BCG vaccination. Nat. Commun. 10, 874 (2019).","journal-title":"Nat. Commun."},{"key":"1506_CR12","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1128\/IAI.00828-07","volume":"75","author":"CL Hutchings","year":"2007","unstructured":"Hutchings, C. L., Birkett, A. J., Moore, A. C. & Hill, A. V. Combination of protein and viral vaccines induces potent cellular and humoral immune responses and enhanced protection from murine malaria challenge. Infect. Immun. 75, 5819\u20135826 (2007).","journal-title":"Infect. Immun."},{"key":"1506_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07246-0","volume":"7","author":"A Milicic","year":"2017","unstructured":"Milicic, A. et al. Adjuvanting a viral vectored vaccine against pre-erythrocytic malaria. Sci. Rep. 7, 7284 (2017).","journal-title":"Sci. Rep."},{"key":"1506_CR14","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.1002\/(SICI)1521-4141(199812)28:12<4345::AID-IMMU4345>3.0.CO;2-P","volume":"28","author":"M Plebanski","year":"1998","unstructured":"Plebanski, M. et al. Protection from Plasmodium berghei infection by priming and boosting T cells to a single class I-restricted epitope with recombinant carriers suitable for human use. Eur. J. Immunol. 28, 4345\u20134355 (1998).","journal-title":"Eur. J. Immunol."},{"key":"1506_CR15","doi-asserted-by":"publisher","first-page":"e0268042","DOI":"10.1371\/journal.pone.0268042","volume":"17","author":"P Villanueva","year":"2022","unstructured":"Villanueva, P. et al. The safety of co-administration of Bacille Calmette-Guerin (BCG) and influenza vaccines. PLoS ONE 17, e0268042 (2022).","journal-title":"PLoS ONE"},{"key":"1506_CR16","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1016\/j.chom.2021.10.001","volume":"29","author":"JK Fiege","year":"2021","unstructured":"Fiege, J. K. et al. Mice with diverse microbial exposure histories as a model for preclinical vaccine testing. Cell Host Microbe 29, 1815\u20131827.e1816 (2021).","journal-title":"Cell Host Microbe"},{"key":"1506_CR17","doi-asserted-by":"publisher","first-page":"109930","DOI":"10.1016\/j.clim.2024.109930","volume":"261","author":"I Baydemir","year":"2024","unstructured":"Baydemir, I., Dulfer, E. A., Netea, M. G. & Dominguez-Andres, J. Trained immunity-inducing vaccines: harnessing innate memory for vaccine design and delivery. Clin. Immunol. 261, 109930 (2024).","journal-title":"Clin. Immunol."},{"key":"1506_CR18","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.immuni.2016.08.011","volume":"45","author":"D Fernandez-Ruiz","year":"2016","unstructured":"Fernandez-Ruiz, D. et al. Liver-resident memory CD8(+) T cells form a front-line defense against malaria liver-stage infection. Immunity 45, 889\u2013902 (2016).","journal-title":"Immunity"},{"key":"1506_CR19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.4049\/jimmunol.174.1.277","volume":"174","author":"T Sato","year":"2005","unstructured":"Sato, T. et al. Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver. J. Immunol. 174, 277\u2013283 (2005).","journal-title":"J. Immunol."},{"key":"1506_CR20","doi-asserted-by":"publisher","first-page":"1567111","DOI":"10.3389\/fimmu.2025.1567111","volume":"16","author":"L Torracinta","year":"2025","unstructured":"Torracinta, L., Gogichadze, N. & Tanner, R. Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review. Front. Immunol. 16, 1567111 (2025).","journal-title":"Front. Immunol."},{"key":"1506_CR21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41590-023-01700-0","volume":"25","author":"A Lee","year":"2024","unstructured":"Lee, A. et al. BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance. Nat. Immunol. 25, 41\u201353 (2024).","journal-title":"Nat. Immunol."},{"key":"1506_CR22","doi-asserted-by":"crossref","unstructured":"Reinke, S., Thakur, A., Gartlan, C., Bezbradica, J. S. & Milicic, A. Inflammasome-mediated immunogenicity of clinical and experimental vaccine adjuvants. Vaccines 8, 554 (2020).","DOI":"10.3390\/vaccines8030554"},{"key":"1506_CR23","doi-asserted-by":"publisher","first-page":"108567","DOI":"10.1016\/j.celrep.2020.108567","volume":"33","author":"YO Alexandre","year":"2020","unstructured":"Alexandre, Y. O. et al. Systemic inflammation suppresses lymphoid tissue remodeling and B cell immunity during concomitant local infection. Cell Rep. 33, 108567 (2020).","journal-title":"Cell Rep."},{"key":"1506_CR24","doi-asserted-by":"crossref","unstructured":"Bauer, A., Tatliadim, H. & Halin, C. Leukocyte trafficking in lymphatic vessels. Cold Spring Harb. Perspect. Med. 12, a041186 (2022).","DOI":"10.1101\/cshperspect.a041186"},{"key":"1506_CR25","doi-asserted-by":"crossref","unstructured":"Atasheva, S. & Shayakhmetov, D. M. Cytokine responses to adenovirus and adenovirus vectors. Viruses 14, 888 (2022).","DOI":"10.3390\/v14050888"},{"key":"1506_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-03944-8","volume":"21","author":"J Chen","year":"2023","unstructured":"Chen, J. et al. BCG-induced trained immunity: history, mechanisms and potential applications. J. Transl. Med. 21, 106 (2023).","journal-title":"J. Transl. Med."},{"key":"1506_CR27","doi-asserted-by":"publisher","first-page":"791","DOI":"10.4049\/jimmunol.2200642","volume":"211","author":"A de Araujo","year":"2023","unstructured":"de Araujo, A., de Queiroz, N., Marinho, F. V. & Oliveira, S. C. Bacillus Calmette-Guerin-trained macrophages elicit a protective inflammatory response against the pathogenic bacteria Brucella abortus. J. Immunol. 211, 791\u2013803 (2023).","journal-title":"J. Immunol."},{"key":"1506_CR28","doi-asserted-by":"publisher","first-page":"9590","DOI":"10.1128\/JVI.00740-12","volume":"86","author":"JE Teigler","year":"2012","unstructured":"Teigler, J. E., Iampietro, M. J. & Barouch, D. H. Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys. J. Virol. 86, 9590\u20139598 (2012).","journal-title":"J. Virol."},{"key":"1506_CR29","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1016\/j.tube.2016.09.026","volume":"101S","author":"MB Huante","year":"2016","unstructured":"Huante, M. B. et al. Differential inflammasome activation signatures following intracellular infection of human macrophages with Mycobacterium bovis BCG or Trypanosoma cruzi. Tuberculosis 101S, S35\u2013S44 (2016).","journal-title":"Tuberculosis"},{"key":"1506_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43447-0","volume":"14","author":"KL Hilligan","year":"2023","unstructured":"Hilligan, K. L. et al. Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2. Nat. Commun. 14, 8229 (2023).","journal-title":"Nat. Commun."},{"key":"1506_CR31","doi-asserted-by":"publisher","first-page":"985938","DOI":"10.3389\/fimmu.2022.985938","volume":"13","author":"S Rakshit","year":"2022","unstructured":"Rakshit, S. et al. Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD vaccine-induced immune responses in SARS-CoV-2 seronegative young Indian adults. Front. Immunol. 13, 985938 (2022).","journal-title":"Front. Immunol."},{"key":"1506_CR32","doi-asserted-by":"crossref","unstructured":"Ramos-Martinez, E. et al. Effect of BCG revaccination on occupationally exposed medical personnel vaccinated against SARS-CoV-2. Cells 10, 3179 (2021).","DOI":"10.3390\/cells10113179"},{"key":"1506_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/srep46621","volume":"7","author":"KA Collins","year":"2017","unstructured":"Collins, K. A., Snaith, R., Cottingham, M. G., Gilbert, S. C. & Hill, A. V. S. Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine. Sci. Rep. 7, 46621 (2017).","journal-title":"Sci. Rep."},{"key":"1506_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23173-1","volume":"12","author":"AJ Spencer","year":"2021","unstructured":"Spencer, A. J. et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat. Commun. 12, 2893 (2021).","journal-title":"Nat. Commun."},{"key":"1506_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-4","volume":"10","author":"ML Visciano","year":"2012","unstructured":"Visciano, M. L., Tagliamonte, M., Tornesello, M. L., Buonaguro, F. M. & Buonaguro, L. Effects of adjuvants on IgG subclasses elicited by virus-like particles. J. Transl. Med. 10, 4 (2012).","journal-title":"J. Transl. Med."},{"key":"1506_CR36","doi-asserted-by":"publisher","first-page":"101245","DOI":"10.1016\/j.xcrm.2023.101245","volume":"4","author":"S Reinke","year":"2023","unstructured":"Reinke, S. et al. Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms. Cell Rep. Med. 4, 101245 (2023).","journal-title":"Cell Rep. Med."}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01506-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01506-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01506-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:06:39Z","timestamp":1791821199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01506-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1506"],"URL":"https:\/\/doi.org\/10.1038\/s41541-026-01506-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7858925\/v1","asserted-by":"object"}]},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"assertion":[{"value":"14 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","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","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"191"}}