{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:17:46Z","timestamp":1785410266674,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Project Program of Jiangsu Key Laboratory of Zoonosis","award":["R2104"],"award-info":[{"award-number":["R2104"]}]},{"name":"Open Project of Key Laboratory of Animal Biopharmaceutical Corps","award":["FM0F2024001"],"award-info":[{"award-number":["FM0F2024001"]}]},{"name":"Shihezi University Research Startup Program for High-Level Talents","award":["RCZK202573"],"award-info":[{"award-number":["RCZK202573"]}]},{"award":["RCZK202573"],"award-info":[{"award-number":["RCZK202573"]}],"id":[{"id":"https:\/\/ror.org\/04x0kvm78","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Youth Outstanding Science and Technology Talent Project of Department of Education of Guizhou Province","award":["QJJ[2024]347"],"award-info":[{"award-number":["QJJ[2024]347"]}]},{"name":"Tongren Science and Technology Bureau Project","award":["TSKY[2023]39"],"award-info":[{"award-number":["TSKY[2023]39"]}]},{"name":"Tongren Science and Technology Bureau Project","award":["TSKY[2024]6"],"award-info":[{"award-number":["TSKY[2024]6"]}]},{"name":"Sichuan Regional Innovation Cooperation Project","award":["2026YFHZ0179"],"award-info":[{"award-number":["2026YFHZ0179"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Brucellosis remains a major zoonotic disease that affects both public health and animal production worldwide. Conventional live vaccines, including S19, RB51, and A19, are commonly used for disease control; however, concerns regarding their safety and performance under field conditions limit their application. Targeted gene deletion in Brucella abortus S2308 has generated multiple candidate vaccine strains, but their protection relative to conventional vaccines has not yet been clearly established. We synthesized evidence from 15 mouse studies to compare the protective performance of S2308-derived gene-deletion mutants with that of conventional vaccines. The pooled estimate did not show a statistically significant difference in splenic bacterial burden after challenge between mutant and conventional vaccine groups (mean difference [MD] = 0.38, 95% CI: \u22120.07 to 0.84; p = 0.10), although substantial heterogeneity was observed (I2 = 95.38%). Heterogeneity was partially explained by mouse strain, mouse age, the functional categories of deleted genes, number of deletions, and challenge dose. Mutants targeting signal-regulatory genes tended to be associated with lower splenic bacterial loads than those targeting genes involved in lipopolysaccharide (LPS) biosynthesis. Overall, based on post-challenge splenic bacterial burden, current mouse evidence suggests that S2308-derived gene-deletion mutants may reduce bacterial burden to an extent broadly comparable to that achieved by conventional Brucella vaccines in mice. The observed association between signal regulation-related gene deletions and lower splenic bacterial burden should be regarded as exploratory and requires further validation using broader protective endpoints and studies in natural target hosts.<\/jats:p>","DOI":"10.3390\/microorganisms14071419","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:45:20Z","timestamp":1782722720000},"page":"1419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Meta-Analysis of the Protective Efficacy of Brucella abortus S2308 Gene-Deletion Mutant Vaccines Compared to Conventional Vaccines in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1739-6918","authenticated-orcid":false,"given":"Jing","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7125-4457","authenticated-orcid":false,"given":"Maoyuan","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0215-7507","authenticated-orcid":false,"given":"Rongrong","family":"Ni","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5038-1943","authenticated-orcid":false,"given":"Xufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3129-7600","authenticated-orcid":false,"given":"Qimin","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0901-4082","authenticated-orcid":false,"given":"Mengdi","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5600-928X","authenticated-orcid":false,"given":"Shuqi","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9749-2828","authenticated-orcid":false,"given":"Zeyao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3521-1492","authenticated-orcid":false,"given":"Tianyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0691-5954","authenticated-orcid":false,"given":"Yuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5156-7626","authenticated-orcid":false,"given":"Zhujie","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8230-3875","authenticated-orcid":false,"given":"Junyuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9564-3999","authenticated-orcid":false,"given":"Yanbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-2385","authenticated-orcid":false,"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-4610","authenticated-orcid":false,"given":"Zhongchen","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guizhou Provincial Key Laboratory for Biodiversity Conservation and Utilization in the Fanjing Mountain Region, Tongren University, Tongren 554300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7954-5136","authenticated-orcid":false,"given":"Jihai","family":"Yi","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5320-4953","authenticated-orcid":false,"given":"Yueli","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","unstructured":"WOAH (2026, February 10). Brucellosis. Available online: https:\/\/www.woah.org\/en\/document\/3-01-04_brucellosis\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"126649","DOI":"10.1016\/j.vaccine.2024.126649","article-title":"Systematic review on the effectiveness of Brucella abortus S19 and RB51 vaccine strains in field studies","volume":"45","author":"Andrade","year":"2025","journal-title":"Vaccine"},{"key":"ref_3","first-page":"1044","article-title":"Brucella abortus Vaccines: Use in Control Programs and Immune Response","volume":"4","author":"Dorneles","year":"2017","journal-title":"J. Bacteriol. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110505","DOI":"10.1016\/j.vetmic.2025.110505","article-title":"Molecular epidemiology, immunobiology, genomics and proteomics insights into bovine brucellosis","volume":"305","author":"Prabhakar","year":"2025","journal-title":"Vet. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Esquivel, M., Ruiz-Villalobos, N., Castillo-Zeled\u00f3n, A., Jim\u00e9nez-Rojas, C., Roop, R.M., Comerci, D.J., Barquero-Calvo, E., Chac\u00f3n-D\u00edaz, C., Caswell, C.C., and Baker, K.S. (2016). Brucella abortus Strain 2308 Wisconsin Genome: Importance of the Definition of Reference Strains. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01557"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Blasco, J.M., Moreno, E., Munoz, P.M., Conde-alvarez, R., and Moriyon, I. (2023). A review of three decades of use of the cattle brucellosis rough vaccine Brucella abortus RB51: Myths and facts. BMC Vet. Res., 19.","DOI":"10.1186\/s12917-023-03773-3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.biologicals.2019.11.005","article-title":"Brucella abortus S19 rfbD mutant is highly attenuated, DIVA enable and confers protection against virulent challenge in mice","volume":"63","author":"Lalsiamthara","year":"2020","journal-title":"Biologicals"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13567-015-0199-7","article-title":"Recent advances in Brucella abortus vaccines","volume":"46","author":"Dorneles","year":"2015","journal-title":"Vet. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.vetmic.2012.07.016","article-title":"Vaccination with recombinant flagellar proteins FlgJ and FliN induce protection against Brucella abortus 544 infection in BALB\/c mice","volume":"161","author":"Li","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Heidary, M., Dashtbin, S., Ghanavati, R., Mahdizade Ari, M., Bostanghadiri, N., Darbandi, A., Navidifar, T., and Talebi, M. (2022). Evaluation of Brucellosis Vaccines: A Comprehensive Review. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.925773"},{"key":"ref_11","first-page":"82","article-title":"A Comprehensive Overview of Approved Animal Brucellosis Live Attenuated Vaccines in China and Novel Vaccine Research Direction","volume":"58","author":"Tang","year":"2024","journal-title":"Chin. J. Vet. Drug"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1139\/cjm-2017-0179","article-title":"Brucella melitensis M5-90\u0394bp26 as a potential live vaccine that allows for the distinction between natural infection and immunization","volume":"63","author":"Li","year":"2017","journal-title":"Can. J. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1128\/IAI.01433-09","article-title":"The Brucella abortus phosphoglycerate kinase mutant is highly attenuated and induces protection superior to that of vaccine strain 19 in immunocompromised and immunocompetent mice","volume":"78","author":"Trant","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1128\/IAI.71.6.3261-3271.2003","article-title":"Characterization of Brucella abortus O-polysaccharide and core lipopolysaccharide mutants and demonstration that a complete core is required for rough vaccines to be efficient against Brucella abortus and Brucella ovis in the mouse model","volume":"71","author":"Monreal","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1128\/IAI.70.9.5036-5044.2002","article-title":"Identification and characterization of a Brucella abortus ATP-binding cassette transporter homolog to Rhizobium meliloti ExsA and its role in virulence and protection in mice","volume":"70","author":"Rosinha","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1128\/IAI.02790-14","article-title":"Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice","volume":"83","author":"Campos","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1128\/IAI.71.11.6264-6269.2003","article-title":"Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine","volume":"71","author":"Ugalde","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s12275-014-3689-9","article-title":"A potent Brucella abortus 2308 \u0394ery live vaccine allows for the differentiation between natural and vaccinated infection","volume":"52","author":"Zhang","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1016\/j.vaccine.2005.12.038","article-title":"Increases of efficacy as vaccine against Brucella abortus infection in mice by simultaneous inoculation with avirulent smooth bvrS\/bvrR and rough wbkA mutants","volume":"24","author":"Manterola","year":"2006","journal-title":"Vaccine"},{"key":"ref_20","first-page":"59","article-title":"Evaluation of Virulence and Immunoprotective Efficacy of the clpP Gene-Deleted Mutant of Brucella abortus","volume":"36","author":"Peng","year":"2019","journal-title":"China Anim. Health Insp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.molimm.2020.06.002","article-title":"A safe non-toxic Brucella abortus ghosts induce immune responses and confer protection in BALB\/c mice","volume":"124","author":"Wang","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5627","DOI":"10.1016\/j.vaccine.2010.06.023","article-title":"Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice","volume":"28","author":"Lacerda","year":"2010","journal-title":"Vaccine"},{"key":"ref_23","first-page":"138","article-title":"Studies on protective efficacy and safety of Brucella abortus ATP\/GTP binding protein gene deleted mutant","volume":"18","author":"Wang","year":"2013","journal-title":"J. China Agric. Univ."},{"key":"ref_24","first-page":"158","article-title":"The virulence detection of B. abortus 2308 mutation strain and the immunize effect on Kunming Mice","volume":"34","author":"Zhang","year":"2016","journal-title":"J. Shihezi Univ. Nat. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1128\/CVI.00573-12","article-title":"In vivo differences in the virulence, pathogenicity, and induced protective immunity of wboA mutants from genetically different parent Brucella spp","volume":"20","author":"Wang","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4142\/jvs.2015.16.4.467","article-title":"Immunization of BALB\/c mice with Brucella abortus 2308\u0394wbkA confers protection against wild-type infection","volume":"16","author":"Li","year":"2015","journal-title":"J. Vet. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.micpath.2017.01.043","article-title":"Brucella abortus 2308\u0394NodV\u0394NodW double-mutant is highly attenuated and confers protection against wild-type challenge in BALB\/c mice","volume":"106","author":"Li","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_28","unstructured":"Hayoun, M.A., Muco, E., and Shorman, M. (2026, February 14). Brucellosis, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK441831\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/01652176.2020.1868616","article-title":"Bovine brucellosis\u2014A comprehensive review","volume":"41","author":"Khurana","year":"2021","journal-title":"Vet. Q."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.vetmic.2008.05.003","article-title":"Protection levels in vaccinated heifers with experimental vaccines Brucella abortus M1-luc and INTA 2","volume":"132","author":"Florentino","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.micinf.2006.10.008","article-title":"Brucella abortus bacA mutant induces greater pro-inflammatory cytokines than the wild-type parent strain","volume":"9","author":"Parent","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13567-023-01200-x","article-title":"ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus","volume":"54","author":"Sun","year":"2023","journal-title":"Vet. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Conde-\u00c1lvarez, R., Arce-Gorvel, V., Iriarte, M., Man\u010dek-Keber, M., Barquero-Calvo, E., Palacios-Chaves, L., Chac\u00f3n-D\u00edaz, C., Chaves-Olarte, E., Martirosyan, A., and von Bargen, K. (2012). The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002675"},{"key":"ref_34","first-page":"842","article-title":"Virulence factors of Brucella: A review","volume":"48","author":"Wen","year":"2021","journal-title":"Microbiol. China"},{"key":"ref_35","first-page":"8","article-title":"Overview of Brucellosis Research","volume":"41","author":"Luo","year":"2025","journal-title":"Xinjiang Xumuye"},{"key":"ref_36","first-page":"4863","article-title":"Biosynthesis of Brucella Lipopolysaccharides and Their Biological Functions in Immune Evasion","volume":"56","author":"Wang","year":"2025","journal-title":"Acta Vet. Zootech. Sin."},{"key":"ref_37","first-page":"1575","article-title":"Research Progress in the Virulence Factors and Intracellular Survival Mechanism of Brucella","volume":"56","author":"You","year":"2025","journal-title":"Acta Vet. Zootech. Sin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1016\/j.vaccine.2016.09.004","article-title":"Vaccination with a \u0394norD \u0394znuA Brucella abortus mutant confers potent protection against virulent challenge","volume":"34","author":"Yang","year":"2016","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.vaccine.2009.10.113","article-title":"\u0394znuA\u0394purE Brucella abortus 2308 mutant as a live vaccine candidate","volume":"28","author":"Yang","year":"2010","journal-title":"Vaccine"},{"key":"ref_40","first-page":"e32","article-title":"Efficacy of Brucella abortus S19 and RB51 vaccine strains: A systematic review and meta-analysis","volume":"69","author":"Pereira","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1297-9716-43-29","article-title":"What have we learned from brucellosis in the mouse model?","volume":"43","author":"Grillo","year":"2012","journal-title":"Vet. Res."},{"key":"ref_42","first-page":"80","article-title":"Present situation and hotspots of KM mouse research based on the CiteSpace map of scientific knowledge","volume":"32","author":"Yang","year":"2024","journal-title":"Acta Lab. Anim. Sci. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1177\/0023677216653984","article-title":"Does age matter? The impact of rodent age on study outcomes","volume":"51","author":"Jackson","year":"2017","journal-title":"Lab. Anim."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:37:18Z","timestamp":1782725838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["microorganisms14071419"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14071419","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]}}}