{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:17:57Z","timestamp":1792520277955,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Given brucellosis is a widespread zoonosis in the world, a safe and effective vaccine is urgently needed. Recent trend in vaccine design has shifted to epitope-based vaccines that are safe and specific. In this study, peptide containing both T-cell and B-cell epitopes of OMP31 was synthesized and used to immunize the mice by nasal administration. The protective efficacy was evaluated. Mice immunized with the B epitope or TB epitope peptides of OMP31 had higher levels of IgG1 and IgG2a in the serum. While the BALB\/c mice immunized with peptides containing T cell epitope or TB epitope of OMP31 showed high degree of IFN-\u03b3-producing T cells in the lymphocytes from the respiratory draining lymph nodes and spleen. After intranasally challenged with 5\u2009\u00d7\u200910<jats:sup>5<\/jats:sup>CFU of<jats:italic>Brucella melitensis<\/jats:italic>(strain 16\u2009M), the bacterial loads in lung of the immunized mice were significantly lower than control group. These data demonstrate for the first time that peptides of OMP31 containing T epitope, B epitope or TB epitopes are of high immunogenicity and thus can protect host from<jats:italic>Brucella melitensis<\/jats:italic>infection in lung.<\/jats:p>","DOI":"10.1038\/s41598-019-40084-w","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T11:05:48Z","timestamp":1551783948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Immunogenicity of OMP31 Peptides and Its Protection Against Brucella melitensis Infection in Mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Fengbo","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuntao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"40084_CR1","doi-asserted-by":"crossref","unstructured":"Huy, T. X. et al. Intracellular trafficking modulation by ginsenoside Rg3 inhibits Brucella abortus uptake and intracellular survival within RAW 264.7 cells. J. Microbiol. Biotechnol (2016).","DOI":"10.4014\/jmb.1609.09060"},{"key":"40084_CR2","first-page":"1675","volume":"32","author":"P Pang","year":"2016","unstructured":"Pang, P. et al. Increased serum levels of soluble programmed death-1 (sPD-1) and sPD-ligand 1 in patients infected with Brucella. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32, 1675\u20131678 (2016).","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi."},{"key":"40084_CR3","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.3892\/etm.2016.3688","volume":"12","author":"H Zhang","year":"2016","unstructured":"Zhang, H. et al. Expression and regulation of the ery operon of Brucella melitensis in human trophoblast cells. Exp. Ther. Med 12, 2723\u20132728 (2016).","journal-title":"Exp. Ther. Med"},{"key":"40084_CR4","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3906\/sag-1506-59","volume":"46","author":"M Sofian","year":"2016","unstructured":"Sofian, M. et al. Interlukine-17 and TGF-\u03b2 levels in patients with acute brucellosisbefore and after treatment. Turk. J. Med. Sci. 46, 1348\u20131352 (2016).","journal-title":"Turk. J. Med. Sci."},{"key":"40084_CR5","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1016\/j.ajpath.2015.03.003","volume":"185","author":"P de Figueiredo","year":"2015","unstructured":"de Figueiredo, P. et al. Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions. Am. J. Pathol. 185, 1505\u20131517 (2015).","journal-title":"Am. J. Pathol."},{"key":"40084_CR6","first-page":"13320","volume":"10","author":"P Pan","year":"2017","unstructured":"Pan, P. et al. Bioinformatics analysis of T- and B-combined epitopes of OMP31 protein of Brucella melitensis in Xinjiang, China. Int. J. Clin. Exp. Med. 10, 13320\u201313330 (2017).","journal-title":"Int. J. Clin. Exp. Med."},{"key":"40084_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-015-2242-z","volume":"15","author":"G Tumwine","year":"2015","unstructured":"Tumwine, G. et al. Human brucellosis: sero-prevalence and associated risk factors in agro-pastoral communities of Kiboga District, Central Uganda. BMC. Public. Health. 15, 900 (2015).","journal-title":"BMC. Public. Health."},{"key":"40084_CR8","unstructured":"Pang, P. et al. The changes of sTim-3\/HMGB1 and Spot forming cells of TGF-\u03b2 secreting from peripheral blood mononuclear cell in patients infected with brucella. Chinese Journal of Immunology. 1 (2017)."},{"key":"40084_CR9","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S0378-1135(02)00255-9","volume":"90","author":"GG Schurig","year":"2002","unstructured":"Schurig, G. G. et al. Brucellosis vaccines: past, present and future. Vet. Microbiol. 90, 479\u2013496 (2002).","journal-title":"Vet. Microbiol."},{"key":"40084_CR10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.prevetmed.2011.04.007","volume":"102","author":"J Godfroid","year":"2011","unstructured":"Godfroid, J. et al. Brucellosis at the animal\/ecosystem\/human interface at the beginning of the 21st century. Prev. Vet. Med. 102, 118\u2013131 (2011).","journal-title":"Prev. Vet. Med."},{"key":"40084_CR11","doi-asserted-by":"publisher","first-page":"281","DOI":"10.4142\/jvs.2017.18.S1.281","volume":"18","author":"J Lalsiamthara","year":"2017","unstructured":"Lalsiamthara, J. et al. Development and trial of vaccines against Brucella. J. Vet. Sci. 18, 281\u2013290 (2017).","journal-title":"J. Vet. Sci."},{"key":"40084_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.4137\/DTI.S38458","volume":"10","author":"H Zahroh","year":"2016","unstructured":"Zahroh, H. et al. Immunoinformatics Approach in Designing Epitope-based Vaccine Against Meningitis-inducing Bacteria (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Type b. Drug. Target. Insights. 10, 19\u201329 (2016).","journal-title":"Drug. Target. Insights."},{"key":"40084_CR13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4103\/2277-9175.166137","volume":"4","author":"SK Verma","year":"2015","unstructured":"Verma, S. K. et al. In silico prediction of B- and T- cell epitope on Lassa virus proteins for peptide based subunit vaccine design. Adv. Biomed. Res. 4, 201 (2015).","journal-title":"Adv. Biomed. Res."},{"key":"40084_CR14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ijpharm.2017.05.045","volume":"527","author":"IS Ganda","year":"2017","unstructured":"Ganda, I. S. et al. Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection. Int. J. Pharm. 527, 79\u201391 (2017).","journal-title":"Int. J. Pharm."},{"key":"40084_CR15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.antiviral.2016.03.005","volume":"129","author":"E Blanco","year":"2016","unstructured":"Blanco, E. et al. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide. Antiviral. Res. 129, 74\u201380 (2016).","journal-title":"Antiviral. Res."},{"key":"40084_CR16","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1016\/j.bmc.2018.03.044","volume":"26","author":"ML Carabali-Isajar","year":"2018","unstructured":"Carabali-Isajar, M. L. et al. Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells. Bioorg. Med. Chem. 26, 2401\u20132409 (2018).","journal-title":"Bioorg. Med. Chem."},{"key":"40084_CR17","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.meegid.2017.04.009","volume":"51","author":"M Saadi","year":"2017","unstructured":"Saadi, M. et al. Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches. Infect. Genet. Evol. 51, 227\u2013234 (2017).","journal-title":"Infect. Genet. Evol."},{"key":"40084_CR18","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.3892\/etm.2016.3655","volume":"12","author":"K Zhang","year":"2016","unstructured":"Zhang, K. et al. OMP31 of Brucella melitensis 16M impairs the apoptosis of macrophages triggered by TNF-\u03b1. Exp. Ther. Med. 12, 2783\u20132789 (2016).","journal-title":"Exp. Ther. Med."},{"key":"40084_CR19","first-page":"17530","volume":"8","author":"QL Ma","year":"2015","unstructured":"Ma, Q. L. et al. Brucella outer membrane protein Omp25 induces microglial cells in vitro to secrete inflammatory cytokines and inhibit apoptosis. Int. J. Clin. Exp. Med. 8, 17530\u201317535 (2015).","journal-title":"Int. J. Clin. Exp. Med."},{"key":"40084_CR20","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.rvsc.2015.03.030","volume":"100","author":"L Yao","year":"2015","unstructured":"Yao, L. et al. Immunogenic response to a recombinant pseudorabies virus carrying bp26 gene of Brucella melitensis in Mice. Res. Vet. Sci. 100, 61\u201367 (2015).","journal-title":"Res. Vet. Sci."},{"key":"40084_CR21","doi-asserted-by":"crossref","unstructured":"Sano, G. et al. Characterization and Evaluation of Newly Developed Immune-Chromatographic Method Targeting Mycoplasma pneumoniae Ribosomal Protein L7\/L12. J. Med. Microbiol. 2016 (2016).","DOI":"10.1099\/jmm.0.000336"},{"key":"40084_CR22","doi-asserted-by":"crossref","unstructured":"Francis, N. et al. CtrA Controls Cell Division and Outer Membrane Composition of the Pathogen Brucella abortus. Mol. Microbiol (2016).","DOI":"10.1111\/mmi.13589"},{"key":"40084_CR23","doi-asserted-by":"publisher","first-page":"5532","DOI":"10.1016\/j.vaccine.2015.09.013","volume":"33","author":"A Ghasemi","year":"2015","unstructured":"Ghasemi, A. et al. Simultaneous immunization of mice with Omp31 and TF provides protection against Brucella melitensis infection. Vaccine. 33, 5532\u20135538 (2015).","journal-title":"Vaccine."},{"key":"40084_CR24","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1128\/iai.64.9.3744-3751.1996","volume":"64","author":"N Vizca\u00edno","year":"1996","unstructured":"Vizca\u00edno, N. et al. Cloning, nucleotide sequence, and expression of the Brucella melitensis omp31 gene coding for an immunogenic major outer membrane protein. Infect. Immun. 64, 3744\u20133751 (1996).","journal-title":"Infect. Immun."},{"key":"40084_CR25","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1128\/CVI.00527-14","volume":"21","author":"M Clausse","year":"2014","unstructured":"Clausse, M. Evaluation of the efficacy of outer membrane protein 31 vaccine formulations for protection against Brucella canis in BALB\/c mice. Clin. Vaccine. Immunol. 21, 1689\u20131694 (2014).","journal-title":"Clin. Vaccine. Immunol."},{"key":"40084_CR26","first-page":"350","volume":"18","author":"J Amani","year":"2015","unstructured":"Amani, J. et al. Immune reactivity of sera obtained from brucellosis patients and vaccinated-rabbits to a fusion protein from Brucella melitensis. Iran. J. Basic. Med. Sci. 18, 350\u2013355 (2015).","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"40084_CR27","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1128\/IAI.67.6.2700-2712.1999","volume":"67","author":"N Vizca\u00edno","year":"1999","unstructured":"Vizca\u00edno, N. et al. Molecular characterization of a Brucella species large DNA fragment deleted in Brucella abortus strains: evidence for a locus involved in the synthesis of a Polysaccharide. Infect. Immun. 67, 2700\u20132712 (1999).","journal-title":"Infect. Immun."},{"key":"40084_CR28","first-page":"422","volume":"41","author":"Z Naseri","year":"2016","unstructured":"Naseri, Z. et al. Prevalence of the Most Common Virulence-Associated Genes among Brucella Melitensis Isolates from Human Blood Cultures in Hamadan Province, West of Iran. Iran. J. Med. Sci. 41, 422\u2013429 (2016).","journal-title":"Iran. J. Med. Sci."},{"key":"40084_CR29","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.molimm.2015.04.015","volume":"66","author":"M Golshani","year":"2015","unstructured":"Golshani, M. et al. Improved immunogenicity and protective efficacy of a divalent DNA vaccine encoding Brucella L7\/L12-truncated Omp31 fusion protein by a DNA priming and protein boosting regimen. Mol. Immunol. 66, 384\u2013391 (2015).","journal-title":"Mol. Immunol."},{"key":"40084_CR30","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.molimm.2015.01.009","volume":"65","author":"M Golshani","year":"2015","unstructured":"Golshani, M. et al. Vaccination with recombinant L7\/L12-truncated Omp31 protein induces protection against Brucella infection in BALB\/c mice. Mol. Immunol. 65, 287\u2013292 (2015).","journal-title":"Mol. Immunol."},{"key":"40084_CR31","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.4049\/jimmunol.1302561","volume":"192","author":"MA Vitry","year":"2014","unstructured":"Vitry, M. A. et al. Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis. J. Immunol. 192, 3740\u20133752 (2014).","journal-title":"J. Immunol."},{"key":"40084_CR32","first-page":"6129","volume":"31","author":"M Clausse","year":"2013","unstructured":"Clausse, M. et al. The vaccine candidate BLSOmp31 protects mice against Brucella canis infection. Vaccine. 2013 31, 6129\u20136135 (2013).","journal-title":"Vaccine. 2013"},{"key":"40084_CR33","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.vetmic.2016.10.027","volume":"197","author":"M Golshani","year":"2016","unstructured":"Golshani, M. et al. Comparison of potential protection conferred by three immunization strategies (protein\/protein, DNA\/DNA, and DNA\/protein) against Brucella infection using Omp2b in BALB\/c Mice. Vet. Microbiol. 197, 47\u201352 (2016).","journal-title":"Vet. Microbiol."},{"key":"40084_CR34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.4049\/jimmunol.1601775","volume":"199","author":"PN Boyaka","year":"2017","unstructured":"Boyaka, P. N. et al. Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems. J. Immunol. 199, 9\u201316 (2017).","journal-title":"J. Immunol."},{"key":"40084_CR35","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.4014\/jmb.1512.12046","volume":"26","author":"YB Im","year":"2016","unstructured":"Im, Y. B. et al. Evaluation of Th1\/Th2-Related Immune Response against Recombinant Proteins of Brucella abortus Infection in Mice. J. Microbiol. Biotechnol. 26, 1132\u20131139 (2016).","journal-title":"J. Microbiol. Biotechnol."},{"key":"40084_CR36","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1128\/IAI.02592-14","volume":"83","author":"JS Fahel","year":"2015","unstructured":"Fahel, J. S. et al. 5-Lipoxygenase negatively regulates Th1 response during Brucella abortus infection in mice. Infect. Immun. 83, 1210\u20131216 (2015).","journal-title":"Infect. Immun."},{"key":"40084_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2016.04.016","volume":"175","author":"D Yin","year":"2016","unstructured":"Yin, D. et al. A novel recombinant multi-epitope protein against Brucella melitensis infection. Immunol. Lett. 175, 1\u20137 (2016).","journal-title":"Immunol. Lett."},{"key":"40084_CR38","doi-asserted-by":"publisher","first-page":"7625","DOI":"10.1007\/s00253-015-6787-7","volume":"99","author":"P Afley","year":"2015","unstructured":"Afley, P. et al. Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice. Appl. Microbiol. Biotechnol. 99, 7625\u20137637 (2015).","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"40084_CR39","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1128\/CVI.00254-10","volume":"18","author":"J Qiu","year":"2011","unstructured":"Qiu, J. et al. Intranasal vaccination with the recombinant Listeria monocytogenes \u0394actA prfA* mutant elicits robust systemic and pulmonary cellular responses and secretory mucosal IgA. Clin. Vaccine. Immunol. 18, 640\u2013646 (2011).","journal-title":"Clin. Vaccine. Immunol."},{"key":"40084_CR40","doi-asserted-by":"publisher","first-page":"6617","DOI":"10.2147\/IJN.S146912","volume":"12","author":"X Dai","year":"2017","unstructured":"Dai, X. et al. Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen. Int. J. Nanomedicine. 12, 6617\u20136632 (2017).","journal-title":"Int. J. Nanomedicine."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40084-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40084-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40084-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T11:18:23Z","timestamp":1721042303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40084-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,5]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40084"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40084-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,5]]},"assertion":[{"value":"13 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2019","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","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3512"}}