{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:54:33Z","timestamp":1791806073596,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHN 1150\/4-1"],"award-info":[{"award-number":["SCHN 1150\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Clinical and experimental evidence suggests that the tuberculosis vaccine BCG offers protection against unrelated pathogens including the malaria parasite. Cerebral malaria (CM) is the most severe complication associated with Plasmodium falciparum infection in humans and is responsible for most of the fatalities attributed to malaria. We investigated whether BCG protected C57BL\/6 mice from P. berghei ANKA (PbA)-induced experimental CM (ECM). The majority of PbA-infected mice that were immunized with BCG showed prolonged survival without developing clinical symptoms of ECM. However, this protective effect waned over time and was associated with the recovery of viable BCG from liver and spleen. Intriguingly, BCG-mediated protection from ECM was not associated with a reduction in parasite burden, indicating that BCG immunization did not improve anti-parasite effector mechanisms. Instead, we found a significant reduction in pro-inflammatory mediators and CD8+ T cells in brains of BCG-vaccinated mice. Together these data suggest that brain recruitment of immune cells involved in the pathogenesis of ECM decreased after BCG vaccination. Understanding the mechanisms underlying the protective effects of BCG on PbA-induced ECM can provide a rationale for developing effective adjunctive therapies to reduce the risk of death and brain damage in CM.<\/jats:p>","DOI":"10.3390\/vaccines8040745","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T09:17:58Z","timestamp":1607505478000},"page":"745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["BCG Provides Short-Term Protection from Experimental Cerebral Malaria in Mice"],"prefix":"10.3390","volume":"8","author":[{"given":"Julia","family":"Witschkowski","sequence":"first","affiliation":[{"name":"Junior Research Group Coinfection, Priority Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-8911","authenticated-orcid":false,"given":"Jochen","family":"Behrends","sequence":"additional","affiliation":[{"name":"Core Facility Fluorescence Cytometry, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Frank","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eggers","sequence":"additional","affiliation":[{"name":"Junior Research Group Coinfection, Priority Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"von Borstel","sequence":"additional","affiliation":[{"name":"Junior Research Group Coinfection, Priority Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hertz","sequence":"additional","affiliation":[{"name":"Junior Research Group Coinfection, Priority Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kristin","family":"Mueller","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), TTU Malaria, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca E.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Junior Research Group Coinfection, Priority Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zwerling, A., Behr, M.A., Verma, A., Brewer, T.F., Menzies, D., and Pai, M. (2011). The BCG World Atlas: A database of global BCG vaccination policies and practices. PLoS Med., 8.","DOI":"10.1371\/journal.pmed.1001012"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fimmu.2018.00121","article-title":"Next-Generation Vaccines Based on Bacille Calmette-Guerin","volume":"9","author":"Nieuwenhuizen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.2217\/fmb-2018-0026","article-title":"Heterologous effects of infant BCG vaccination: Potential mechanisms of immunity","volume":"13","author":"Butkeviciute","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1016\/S0264-410X(03)00181-6","article-title":"BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?","volume":"21","author":"Garly","year":"2003","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1136\/bmj.38261.496366.82","article-title":"Non-specific effects of vaccination on child survival: Prospective cohort study in Burkina Faso","volume":"329","author":"Vaugelade","year":"2004","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1136\/bmj.321.7274.1435","article-title":"Routine vaccinations and child survival: Follow up study in Guinea-Bissau, West Africa","volume":"321","author":"Kristensen","year":"2000","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1586\/14760584.5.2.277","article-title":"Bacillus Calmette-Guerin vaccination and infant mortality","volume":"5","author":"Roth","year":"2006","journal-title":"Expert Rev. Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/jir240","article-title":"Randomized trial of BCG vaccination at birth to low-birth-weight children: Beneficial nonspecific effects in the neonatal period?","volume":"204","author":"Aaby","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/ije\/dyh392","article-title":"BCG vaccination scar associated with better childhood survival in Guinea-Bissau","volume":"34","author":"Roth","year":"2005","journal-title":"Int. J. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e001862","DOI":"10.1136\/bmjgh-2019-001862","article-title":"BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa","volume":"4","author":"Berendsen","year":"2019","journal-title":"BMJ Glob. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/iai.33.1.199-211.1981","article-title":"Host defenses in murine malaria: Nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation","volume":"33","author":"Murphy","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0264-410X(00)00257-7","article-title":"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","volume":"19","author":"Matsumoto","year":"2000","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-3024.2007.00983.x","article-title":"BCG-malaria co-Infection has paradoxical effects on C57BL\/6 and A\/J mouse strains","volume":"30","author":"Leisewitz","year":"2008","journal-title":"Parasite Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1128\/iai.31.1.408-412.1981","article-title":"Effect of route of Mycobacterium bovis BCG administration on induction of suppression of sporozoite immunity in rodent malaria","volume":"31","author":"Smrkovski","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.4049\/jimmunol.121.4.1257","article-title":"Rodent malaria: BCG-induced protection and immunosuppression","volume":"121","author":"Smrkovski","year":"1978","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/259309a0","article-title":"Protection of mice against Babesia and Plasmodium with BCG","volume":"259","author":"Clark","year":"1976","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Parra, M., Liu, X., Derrick, S.C., Yang, A., Tian, J., Kolibab, K., Kumar, S., and Morris, S.L. (2013). Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066115"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ni.3178","article-title":"Innate immune memory: A paradigm shift in understanding host defense","volume":"16","author":"Netea","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.molimm.2015.06.019","article-title":"Trained immunity: A smart way to enhance innate immune defence","volume":"68","author":"Joosten","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained immunity: A memory for innate host defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chom.2017.12.010","article-title":"BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity","volume":"23","author":"Arts","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41467-019-08659-3","article-title":"Outcomes of controlled human malaria infection after BCG vaccination","volume":"10","author":"Walk","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4161\/viru.19013","article-title":"Cerebral malaria: Mysteries at the blood-brain barrier","volume":"3","author":"Renia","year":"2012","journal-title":"Virulence"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3389\/fimmu.2018.02016","article-title":"Cerebral Malaria in Mouse and Man","volume":"9","author":"Ghazanfari","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Idro, R., Kakooza-Mwesige, A., Balyejjussa, S., Mirembe, G., Mugasha, C., Tugumisirize, J., and Byarugaba, J. (2010). Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res. Notes, 3.","DOI":"10.1186\/1756-0500-3-104"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1203\/PDR.0b013e3181eee738","article-title":"Cerebral malaria: Mechanisms of brain injury and strategies for improved neurocognitive outcome","volume":"68","author":"Idro","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijpara.2010.08.003","article-title":"Coincident parasite and CD8 T cell sequestration is required for development of experimental cerebral malaria","volume":"41","author":"McQuillan","year":"2011","journal-title":"Int. J. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1128\/IAI.73.9.5645-5653.2005","article-title":"Early cytokine production is associated with protection from murine cerebral malaria","volume":"73","author":"Mitchell","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1128\/IAI.00079-10","article-title":"Accumulation of Plasmodium berghei-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice","volume":"78","author":"Baptista","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.4049\/jimmunol.1003955","article-title":"Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria","volume":"186","author":"Haque","year":"2011","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1128\/IAI.01259-13","article-title":"Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria","volume":"82","author":"Settles","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/0035-9203(82)90203-6","article-title":"Cerebral malaria in inbred mice. I. A new model and its pathology","volume":"76","author":"Rest","year":"1982","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Carroll, R.W., Wainwright, M.S., Kim, K.Y., Kidambi, T., Gomez, N.D., Taylor, T., and Haldar, K. (2010). A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013124"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1128\/IAI.01290-15","article-title":"Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL\/6 Mice","volume":"84","author":"Blank","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1038\/s41598-018-21551-2","article-title":"Protection from experimental cerebral malaria with a single intravenous or subcutaneous whole-parasite immunization","volume":"8","author":"Heiss","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/emmm.201202273","article-title":"Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria","volume":"5","author":"Howland","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3389\/fimmu.2019.00830","article-title":"The Ins and Outs of Cerebral Malaria Pathogenesis: Immunopathology, Extracellular Vesicles, Immunometabolism, and Trained Immunity","volume":"10","author":"Sierro","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3389\/fcimb.2017.00324","article-title":"Cytokines and Chemokines in Cerebral Malaria Pathogenesis","volume":"7","author":"Dunst","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.pt.2019.04.010","article-title":"Blood-Brain Barrier in Cerebral Malaria: Pathogenesis and Therapeutic Intervention","volume":"35","author":"Nishanth","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"968","DOI":"10.4049\/jimmunol.1200688","article-title":"IFN-gamma-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain","volume":"189","author":"Greig","year":"2012","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.4049\/jimmunol.169.11.6369","article-title":"On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria","volume":"169","author":"Belnoue","year":"2002","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.3389\/fimmu.2018.02611","article-title":"HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage","volume":"9","author":"Muscate","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.3389\/fimmu.2018.02869","article-title":"Non-specific Effects of Vaccines Illustrated Through the BCG Example: From Observations to Demonstrations","volume":"9","author":"Uthayakumar","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/iai.25.1.310-319.1979","article-title":"Immunosuppressive activity of BCG. effects of adjuvant disease, lymphocyte subpopulations, and homing of thoracic duct cells in rats","volume":"25","author":"Sutherland","year":"1979","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1073\/pnas.75.10.5142","article-title":"Systemic bacillus Calmette-Guerin (BCG) activates natural suppressor cells","volume":"75","author":"Bennett","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","first-page":"1","article-title":"BCG and protection against inflammatory and auto-immune diseases","volume":"16","author":"Locht","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1212\/WNL.53.7.1588","article-title":"Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis","volume":"53","author":"Ristori","year":"1999","journal-title":"Neurology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1212\/01.wnl.0000438216.93319.ab","article-title":"Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS","volume":"82","author":"Ristori","year":"2014","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.3389\/fimmu.2018.02777","article-title":"Extended Freeze-Dried BCG Instructed pDCs Induce Suppressive Tregs and Dampen EAE","volume":"9","author":"Lippens","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/jnr.23253","article-title":"Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson\u2019s disease","volume":"91","author":"Lacan","year":"2013","journal-title":"J. Neurosci. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yong, J., Lacan, G., Dang, H., Hsieh, T., Middleton, B., Wasserfall, C., Tian, J., Melega, W.P., and Kaufman, D.L. (2011). BCG vaccine-induced neuroprotection in a mouse model of Parkinson\u2019s disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016610"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.nbd.2017.02.001","article-title":"Immunization with Bacillus Calmette-Guerin (BCG) alleviates neuroinflammation and cognitive deficits in APP\/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain","volume":"101","author":"Zuo","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1172\/JCI133935","article-title":"BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner","volume":"130","author":"Koeken","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1084\/jem.20020128","article-title":"Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria","volume":"195","author":"Engwerda","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0","article-title":"Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection","volume":"30","author":"Amani","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.1073\/pnas.86.14.5572","article-title":"Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor","volume":"86","author":"Grau","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/sj.mn.7800159","article-title":"Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria","volume":"9","author":"Bauer","year":"2002","journal-title":"Microcirculation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1462-5822.2011.01741.x","article-title":"The role of the spleen in malaria","volume":"14","author":"Ferrer","year":"2012","journal-title":"Cell Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.3389\/fimmu.2018.03157","article-title":"PDL1 Fusion Protein Protects Against Experimental Cerebral Malaria via Repressing Over-Reactive CD8(+) T Cell Responses","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1093\/infdis\/137.5.550","article-title":"Conditions for bacille Calmette-Guerin-induced resistance to infection with Schistosoma mansoni in mice","volume":"137","author":"Civil","year":"1978","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1084\/jem.129.5.1079","article-title":"The host response to Calmette-Guerin bacillus infection in mice","volume":"129","author":"Blanden","year":"1969","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6911","DOI":"10.1016\/j.vaccine.2014.10.041","article-title":"Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis","volume":"32","author":"Kaveh","year":"2014","journal-title":"Vaccine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.0300-9475.2004.01471.x","article-title":"The influence of remaining live BCG organisms in vaccinated mice on the maintenance of immunity to tuberculosis","volume":"60","author":"Olsen","year":"2004","journal-title":"Scand. J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Converse, P.J., Almeida, D.V., Nuermberger, E.L., and Grosset, J.H. (2011). BCG-mediated protection against Mycobacterium ulcerans infection in the mouse. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0000985"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/745\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:42:38Z","timestamp":1760179358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,9]]},"references-count":66,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["vaccines8040745"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8040745","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,9]]}}}