{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:39:49Z","timestamp":1792543189612,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":90,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1800905"],"award-info":[{"award-number":["2022YFD1800905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"DOI":"10.1186\/s12917-026-05751-x","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:55:59Z","timestamp":1784775359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhalable epitope vaccine 1022-SpaA V3 establishes nasal mucosal fortress against zoonotic Streptococcus suis"],"prefix":"10.1186","volume":"22","author":[{"given":"Hong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikun","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liancheng","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9447-6908","authenticated-orcid":false,"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"5751_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9050374","author":"M Segura","year":"2020","unstructured":"Segura M, et al. Update on Streptococcus suis research and prevention in the era of antimicrobial restriction: 4th International Workshop on S. suis. Pathogens. 2020. https:\/\/doi.org\/10.3390\/pathogens9050374.","journal-title":"Pathogens"},{"key":"5751_CR2","doi-asserted-by":"publisher","first-page":"3772","DOI":"10.1002\/1873-3468.12364","volume":"590","author":"M Segura","year":"2016","unstructured":"Segura M, Calzas C, Grenier D, Gottschalk M. Initial steps of the pathogenesis of the infection caused by Streptococcus suis: fighting against nonspecific defenses. FEBS Lett. 2016;590:3772\u201399. https:\/\/doi.org\/10.1002\/1873-3468.12364.","journal-title":"FEBS Lett"},{"key":"5751_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2020.108750","volume":"247","author":"C Zhang","year":"2020","unstructured":"Zhang C, et al. Capsular serotypes, antimicrobial susceptibility, and the presence of transferable oxazolidinone resistance genes in Streptococcus suis isolated from healthy pigs in China. Vet Microbiol. 2020;247:108750. https:\/\/doi.org\/10.1016\/j.vetmic.2020.108750.","journal-title":"Vet Microbiol"},{"key":"5751_CR4","doi-asserted-by":"publisher","first-page":"186","DOI":"10.26444\/aaem\/85651","volume":"25","author":"J Dutkiewicz","year":"2018","unstructured":"Dutkiewicz J, et al. Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II - Pathogenesis. Ann Agric Environ Med. 2018;25:186\u2013203. https:\/\/doi.org\/10.26444\/aaem\/85651.","journal-title":"Ann Agric Environ Med"},{"key":"5751_CR5","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/s1473-3099(07)70001-4","volume":"7","author":"ZR Lun","year":"2007","unstructured":"Lun ZR, Wang QP, Chen XG, Li AX, Zhu XQ. Streptococcus suis: an emerging zoonotic pathogen. Lancet Infect Dis. 2007;7:201\u20139. https:\/\/doi.org\/10.1016\/s1473-3099(07)70001-4.","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"5751_CR6","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41541-024-01015-7","volume":"9","author":"J Liu","year":"2024","unstructured":"Liu J, et al. A multi-epitope subunit vaccine providing broad cross-protection against diverse serotypes of Streptococcus suis. NPJ Vaccines. 2024;9:216. https:\/\/doi.org\/10.1038\/s41541-024-01015-7.","journal-title":"NPJ Vaccines"},{"key":"5751_CR7","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1136\/jcp.2004.016253","volume":"57","author":"Q Zhang","year":"2004","unstructured":"Zhang Q, Finn A. Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria. J Clin Pathol. 2004;57:1015\u201321. https:\/\/doi.org\/10.1136\/jcp.2004.016253.","journal-title":"J Clin Pathol"},{"key":"5751_CR8","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.vaccine.2011.12.035","volume":"30","author":"CN Dekker","year":"2012","unstructured":"Dekker CN, et al. Homologous whole bacterin vaccination is not able to reduce Streptococcus suis serotype 9 strain 7997 transmission among pigs or colonization. Vaccine. 2012;30:1379\u201387. https:\/\/doi.org\/10.1016\/j.vaccine.2011.12.035.","journal-title":"Vaccine"},{"key":"5751_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-021-01004-x","volume":"52","author":"MR Obradovic","year":"2021","unstructured":"Obradovic MR, Corsaut L, Dolbec D, Gottschalk M, Segura M. Experimental evaluation of protection and immunogenicity of Streptococcus suis bacterin-based vaccines formulated with different commercial adjuvants in weaned piglets. Vet Res. 2021;52:133. https:\/\/doi.org\/10.1186\/s13567-021-01004-x.","journal-title":"Vet Res"},{"key":"5751_CR10","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1586\/14760584.2015.1101349","volume":"14","author":"M Segura","year":"2015","unstructured":"Segura M. Streptococcus suis vaccines: candidate antigens and progress. Expert Rev Vaccines. 2015;14:1587\u2013608. https:\/\/doi.org\/10.1586\/14760584.2015.1101349.","journal-title":"Expert Rev Vaccines"},{"key":"5751_CR11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/bs.ampbs.2020.12.002","volume":"78","author":"G Tram","year":"2021","unstructured":"Tram G, Jennings MP, Blackall PJ, Atack JM. Streptococcus suis pathogenesis-A diverse array of virulence factors for a zoonotic lifestyle. Adv Microb Physiol. 2021;78:217\u201357. https:\/\/doi.org\/10.1016\/bs.ampbs.2020.12.002.","journal-title":"Adv Microb Physiol"},{"key":"5751_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087442","author":"T Gao","year":"2023","unstructured":"Gao T, et al. Theaflavin ameliorates Streptococcus suis-induced infection in vitro and in vivo. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24087442.","journal-title":"Int J Mol Sci"},{"key":"5751_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19887-3","volume":"11","author":"Z Wang","year":"2020","unstructured":"Wang Z, et al. Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease. Nat Commun. 2020;11:6063. https:\/\/doi.org\/10.1038\/s41467-020-19887-3.","journal-title":"Nat Commun"},{"key":"5751_CR14","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.micinf.2015.12.005","volume":"18","author":"L Fu","year":"2016","unstructured":"Fu L, et al. Characterization of IgA1 protease as a surface protective antigen of Streptococcus suis serotype 2. Microbes Infect. 2016;18:285\u20139. https:\/\/doi.org\/10.1016\/j.micinf.2015.12.005.","journal-title":"Microbes Infect"},{"key":"5751_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12121355","author":"Y Prokopenko","year":"2024","unstructured":"Prokopenko Y, et al. Protective antimicrobial effect of the potential vaccine created on the basis of the structure of the IgA1 protease from Neisseria meningitidis. Vaccines. 2024. https:\/\/doi.org\/10.3390\/vaccines12121355.","journal-title":"Vaccines"},{"issue":"3","key":"5751_CR16","doi-asserted-by":"publisher","first-page":"e0055022","DOI":"10.1128\/mbio.00550-22","volume":"13","author":"M Kilian","year":"2022","unstructured":"Kilian M, et al. Induction of susceptibility to disseminated infection with IgA1 protease-producing encapsulated pathogens Streptococcus pneumoniae, Haemophilus influenzae Type b, and Neisseria meningitidis. mBio. 2022;13:e0055022. https:\/\/doi.org\/10.1128\/mbio.00550-22.","journal-title":"mBio"},{"key":"5751_CR17","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1128\/iai.26.1.254-261.1979","volume":"26","author":"CJ Male","year":"1979","unstructured":"Male CJ. Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae. Infect Immun. 1979;26:254\u201361. https:\/\/doi.org\/10.1128\/iai.26.1.254-261.1979.","journal-title":"Infect Immun"},{"key":"5751_CR18","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.vetmic.2010.09.024","volume":"148","author":"L Bonifait","year":"2011","unstructured":"Bonifait L, Vaillancourt K, Gottschalk M, Frenette M, Grenier D. Purification and characterization of the subtilisin-like protease of Streptococcus suis that contributes to its virulence. Vet Microbiol. 2011;148:333\u201340. https:\/\/doi.org\/10.1016\/j.vetmic.2010.09.024.","journal-title":"Vet Microbiol"},{"key":"5751_CR19","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v6.26189","volume":"6","author":"G Conrads","year":"2014","unstructured":"Conrads G, et al. Comparing the cariogenic species Streptococcus sobrinus and S. mutans on whole genome level. J Oral Microbiol. 2014;6:26189. https:\/\/doi.org\/10.3402\/jom.v6.26189.","journal-title":"J Oral Microbiol"},{"key":"5751_CR20","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1128\/cvi.00099-07","volume":"14","author":"H To","year":"2007","unstructured":"To H, Nagai S. Genetic and antigenic diversity of the surface protective antigen proteins of Erysipelothrix rhusiopathiae. Clin Vaccine Immunol. 2007;14:813\u201320. https:\/\/doi.org\/10.1128\/cvi.00099-07.","journal-title":"Clin Vaccine Immunol"},{"key":"5751_CR21","doi-asserted-by":"publisher","first-page":"101745","DOI":"10.1016\/j.jbc.2022.101745","volume":"298","author":"MSG Legg","year":"2022","unstructured":"Legg MSG, et al. The S-layer homology domains of Paenibacillus alvei surface protein SpaA bind to cell wall polysaccharide through the terminal monosaccharide residue. J Biol Chem. 2022;298:101745. https:\/\/doi.org\/10.1016\/j.jbc.2022.101745.","journal-title":"J Biol Chem"},{"key":"5751_CR22","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1128\/iai.58.7.2276-2282.1990","volume":"58","author":"RM Goldschmidt","year":"1990","unstructured":"Goldschmidt RM, Curtiss R 3rd. Cross-reactivity between the immunodominant determinant of the antigen I component of Streptococcus sobrinus SpaA protein and surface antigens from other members of the Streptococcus mutans group. Infect Immun. 1990;58:2276\u201382. https:\/\/doi.org\/10.1128\/iai.58.7.2276-2282.1990.","journal-title":"Infect Immun"},{"key":"5751_CR23","first-page":"3","volume":"36","author":"R Curtiss 3rd","year":"1987","unstructured":"Curtiss R 3rd, Pearce C, Pollack J, Murchison HM. Isolation and characterization of mutants of Streptococcus mutans using selective removal of wild-type cells by agglutination with an agglutinin from Persea americana. Acta Microbiol Pol. 1987;36:3\u201315.","journal-title":"Acta Microbiol Pol"},{"key":"5751_CR24","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1093\/infdis\/jiz352","volume":"220","author":"X Xing","year":"2019","unstructured":"Xing X, et al. Intranasal Vaccination With Multiple Virulence Factors Promotes Mucosal Clearance of Streptococcus suis Across Serotypes and Protects Against Meningitis in Mice. J Infect Dis. 2019;220:1679\u201387. https:\/\/doi.org\/10.1093\/infdis\/jiz352.","journal-title":"J Infect Dis"},{"key":"5751_CR25","doi-asserted-by":"publisher","first-page":"D436","DOI":"10.1093\/nar\/gkae1092","volume":"53","author":"R Vita","year":"2025","unstructured":"Vita R, et al. The Immune Epitope Database (IEDB): 2024 update. Nucleic Acids Res. 2025;53:D436\u201343. https:\/\/doi.org\/10.1093\/nar\/gkae1092.","journal-title":"Nucleic Acids Res"},{"key":"5751_CR26","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/imm.12889","volume":"154","author":"KK Jensen","year":"2018","unstructured":"Jensen KK, et al. Improved methods for predicting peptide binding affinity to MHC class II molecules. Immunology. 2018;154:394\u2013406. https:\/\/doi.org\/10.1111\/imm.12889.","journal-title":"Immunology"},{"key":"5751_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1699-0463.1993.tb00073.x","volume":"101","author":"CW Czarniecki","year":"1993","unstructured":"Czarniecki CW, Sonnenfeld G. Interferon-gamma and resistance to bacterial infections. Apmis. 1993;101:1\u201317. https:\/\/doi.org\/10.1111\/j.1699-0463.1993.tb00073.x.","journal-title":"Apmis"},{"key":"5751_CR28","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12974-025-03376-9","volume":"22","author":"Z Van Roy","year":"2025","unstructured":"Van Roy Z, Kak G, Fallet RW, Kielian T. Interferon-gamma receptor signaling regulates innate immunity during Staphylococcus aureus craniotomy infection. J Neuroinflammation. 2025;22:46. https:\/\/doi.org\/10.1186\/s12974-025-03376-9.","journal-title":"J Neuroinflammation"},{"key":"5751_CR29","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/jmr.893","volume":"21","author":"Y El-Manzalawy","year":"2008","unstructured":"El-Manzalawy Y, Dobbs D, Honavar V. Predicting linear B-cell epitopes using string kernels. J Mol Recognit. 2008;21:243\u201355. https:\/\/doi.org\/10.1002\/jmr.893.","journal-title":"J Mol Recognit"},{"key":"5751_CR30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/prot.21078","volume":"65","author":"S Saha","year":"2006","unstructured":"Saha S, Raghava GP. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins. 2006;65:40\u20138. https:\/\/doi.org\/10.1002\/prot.21078.","journal-title":"Proteins"},{"key":"5751_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-4","volume":"8","author":"IA Doytchinova","year":"2007","unstructured":"Doytchinova IA, Flower DR. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics. 2007;8:4. https:\/\/doi.org\/10.1186\/1471-2105-8-4.","journal-title":"BMC Bioinformatics"},{"key":"5751_CR32","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.jaci.2022.01.016","volume":"149","author":"MH Shamji","year":"2022","unstructured":"Shamji MH, et al. Diverse immune mechanisms of allergen immunotherapy for allergic rhinitis with and without asthma. J Allergy Clin Immunol. 2022;149:791\u2013801. https:\/\/doi.org\/10.1016\/j.jaci.2022.01.016.","journal-title":"J Allergy Clin Immunol"},{"key":"5751_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.136827","volume":"282","author":"Y Li","year":"2024","unstructured":"Li Y, et al. A review on the development of bacterial multi-epitope recombinant protein vaccines via reverse vaccinology. Int J Biol Macromol. 2024;282:136827. https:\/\/doi.org\/10.1016\/j.ijbiomac.2024.136827.","journal-title":"Int J Biol Macromol"},{"key":"5751_CR34","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jaci.2008.04.022","volume":"122","author":"KO Kisich","year":"2008","unstructured":"Kisich KO, Carspecken CW, Fi\u00e9ve S, Boguniewicz M, Leung DY. Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3. J Allergy Clin Immunol. 2008;122:62\u20138. https:\/\/doi.org\/10.1016\/j.jaci.2008.04.022.","journal-title":"J Allergy Clin Immunol"},{"key":"5751_CR35","doi-asserted-by":"publisher","first-page":"359","DOI":"10.34172\/bi.2022.23769","volume":"12","author":"Y Ysrafil","year":"2022","unstructured":"Ysrafil Y, et al. Designing multi-epitope based peptide vaccine candidates against SARS-CoV-2 using immunoinformatics approach. Bioimpacts. 2022;12:359\u201370. https:\/\/doi.org\/10.34172\/bi.2022.23769.","journal-title":"Bioimpacts"},{"key":"5751_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-66858-5","volume":"14","author":"G Sethi","year":"2024","unstructured":"Sethi G, et al. Immunoinformatics and structural aided approach to develop multi-epitope based subunit vaccine against Mycobacterium tuberculosis. Sci Rep. 2024;14:15923. https:\/\/doi.org\/10.1038\/s41598-024-66858-5.","journal-title":"Sci Rep"},{"key":"5751_CR37","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1042\/bcj20160575","volume":"473","author":"D Zalem","year":"2016","unstructured":"Zalem D, et al. Biochemical and structural characterization of the novel sialic acid-binding site of Escherichia coli heat-labile enterotoxin LT-IIb. Biochem J. 2016;473:3923\u201336. https:\/\/doi.org\/10.1042\/bcj20160575.","journal-title":"Biochem J"},{"key":"5751_CR38","doi-asserted-by":"publisher","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","volume":"33","author":"M Hebditch","year":"2017","unstructured":"Hebditch M, Carballo-Amador MA, Charonis S, Curtis R, Warwicker J. Protein-Sol: a web tool for predicting protein solubility from sequence. Bioinformatics. 2017;33:3098\u2013100. https:\/\/doi.org\/10.1093\/bioinformatics\/btx345.","journal-title":"Bioinformatics"},{"key":"5751_CR39","doi-asserted-by":"publisher","first-page":"W349","DOI":"10.1093\/nar\/gkt381","volume":"41","author":"DW Buchan","year":"2013","unstructured":"Buchan DW, Minneci F, Nugent TC, Bryson K, Jones DT. Scalable web services for the PSIPRED Protein Analysis Workbench. Nucleic Acids Res. 2013;41:W349\u2013357. https:\/\/doi.org\/10.1093\/nar\/gkt381.","journal-title":"Nucleic Acids Res"},{"key":"5751_CR40","doi-asserted-by":"publisher","first-page":"W407","DOI":"10.1093\/nar\/gkm290","volume":"35","author":"M Wiederstein","year":"2007","unstructured":"Wiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 2007;35:W407\u2013410. https:\/\/doi.org\/10.1093\/nar\/gkm290.","journal-title":"Nucleic Acids Res"},{"key":"5751_CR41","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1002\/pro.5560020916","volume":"2","author":"C Colovos","year":"1993","unstructured":"Colovos C, Yeates TO. Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci. 1993;2:1511\u20139. https:\/\/doi.org\/10.1002\/pro.5560020916.","journal-title":"Protein Sci"},{"key":"5751_CR42","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1186\/1471-2105-9-514","volume":"9","author":"J Ponomarenko","year":"2008","unstructured":"Ponomarenko J, et al. ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinformatics. 2008;9:514. https:\/\/doi.org\/10.1186\/1471-2105-9-514.","journal-title":"BMC Bioinformatics"},{"key":"5751_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1239142","volume":"14","author":"Y Yang","year":"2023","unstructured":"Yang Y, et al. cGAS-STING signaling pathway in intestinal homeostasis and diseases. Front Immunol. 2023;14:1239142. https:\/\/doi.org\/10.3389\/fimmu.2023.1239142.","journal-title":"Front Immunol"},{"key":"5751_CR44","doi-asserted-by":"publisher","first-page":"W322","DOI":"10.1093\/nar\/gkz397","volume":"47","author":"G Weng","year":"2019","unstructured":"Weng G, et al. HawkDock: a web server to predict and analyze the protein-protein complex based on computational docking and MM\/GBSA. Nucleic Acids Res. 2019;47:W322\u201330. https:\/\/doi.org\/10.1093\/nar\/gkz397.","journal-title":"Nucleic Acids Res"},{"key":"5751_CR45","doi-asserted-by":"publisher","first-page":"6037","DOI":"10.1021\/acs.jctc.3c00714","volume":"19","author":"G Oanca","year":"2023","unstructured":"Oanca G, van der Ent F, \u00c5qvist J. Efficient empirical valence bond simulations with GROMACS. J Chem Theory Comput. 2023;19:6037\u201345. https:\/\/doi.org\/10.1021\/acs.jctc.3c00714.","journal-title":"J Chem Theory Comput"},{"key":"5751_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009862","volume":"5","author":"N Rapin","year":"2010","unstructured":"Rapin N, Lund O, Bernaschi M, Castiglione F. Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PLoS One. 2010;5:e9862. https:\/\/doi.org\/10.1371\/journal.pone.0009862.","journal-title":"PLoS One"},{"key":"5751_CR47","doi-asserted-by":"publisher","first-page":"W526","DOI":"10.1093\/nar\/gki376","volume":"33","author":"A Grote","year":"2005","unstructured":"Grote A, et al. JCat: a novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res. 2005;33:W526\u2013531. https:\/\/doi.org\/10.1093\/nar\/gki376.","journal-title":"Nucleic Acids Res"},{"key":"5751_CR48","doi-asserted-by":"publisher","first-page":"10522","DOI":"10.1021\/acs.nanolett.3c03419","volume":"23","author":"Y Xu","year":"2023","unstructured":"Xu Y, et al. Transmucosal delivery of nasal nanovaccines enhancing mucosal and systemic immunity. Nano Lett. 2023;23:10522\u201331. https:\/\/doi.org\/10.1021\/acs.nanolett.3c03419.","journal-title":"Nano Lett"},{"key":"5751_CR49","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41586-023-06809-8","volume":"624","author":"T Ye","year":"2023","unstructured":"Ye T, et al. Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization. Nature. 2023;624:630\u20138. https:\/\/doi.org\/10.1038\/s41586-023-06809-8.","journal-title":"Nature"},{"key":"5751_CR50","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40813-020-00150-6","volume":"6","author":"K Rieckmann","year":"2020","unstructured":"Rieckmann K, Pendzialek SM, Vahlenkamp T, Baums CG. A critical review speculating on the protective efficacies of autogenous Streptococcus suis bacterins as used in Europe. Porcine Health Manag. 2020;6:12. https:\/\/doi.org\/10.1186\/s40813-020-00150-6.","journal-title":"Porcine Health Manag"},{"key":"5751_CR51","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nrc2373","volume":"8","author":"CJ Melief","year":"2008","unstructured":"Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer. 2008;8:351\u201360. https:\/\/doi.org\/10.1038\/nrc2373.","journal-title":"Nat Rev Cancer"},{"key":"5751_CR52","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1002\/eji.201343324","volume":"43","author":"RA Rosalia","year":"2013","unstructured":"Rosalia RA, et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation. Eur J Immunol. 2013;43:2554\u201365. https:\/\/doi.org\/10.1002\/eji.201343324.","journal-title":"Eur J Immunol"},{"key":"5751_CR53","doi-asserted-by":"publisher","first-page":"e1008237","DOI":"10.1371\/journal.pcbi.1008237","volume":"16","author":"E Dorigatti","year":"2020","unstructured":"Dorigatti E, Schubert B. Graph-theoretical formulation of the generalized epitope-based vaccine design problem. PLoS Comput Biol. 2020;16:e1008237. https:\/\/doi.org\/10.1371\/journal.pcbi.1008237.","journal-title":"PLoS Comput Biol"},{"key":"5751_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2025.111346","volume":"86","author":"S Mandal","year":"2025","unstructured":"Mandal S, et al. Development of a multi-epitope vaccine candidate targeting blood-stage of malaria through immunoinformatics approach. Hum Immunol. 2025;86:111346. https:\/\/doi.org\/10.1016\/j.humimm.2025.111346.","journal-title":"Hum Immunol"},{"key":"5751_CR55","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.coi.2016.06.007","volume":"41","author":"SG Reed","year":"2016","unstructured":"Reed SG, Hsu FC, Carter D, Orr MT. The science of vaccine adjuvants: advances in TLR4 ligand adjuvants. Curr Opin Immunol. 2016;41:85\u201390. https:\/\/doi.org\/10.1016\/j.coi.2016.06.007.","journal-title":"Curr Opin Immunol"},{"key":"5751_CR56","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1517\/14712598.4.7.1129","volume":"4","author":"JR Baldridge","year":"2004","unstructured":"Baldridge JR, et al. Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents. Expert Opin Biol Ther. 2004;4:1129\u201338. https:\/\/doi.org\/10.1517\/14712598.4.7.1129.","journal-title":"Expert Opin Biol Ther"},{"key":"5751_CR57","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41590-025-02156-0","volume":"26","author":"DI Kwon","year":"2025","unstructured":"Kwon DI, et al. Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice. Nat Immunol. 2025;26:908\u201319. https:\/\/doi.org\/10.1038\/s41590-025-02156-0.","journal-title":"Nat Immunol"},{"key":"5751_CR58","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S441302","author":"C Miao","year":"2023","unstructured":"Miao C, et al. Immunoinformatics prediction and protective efficacy of vaccine candidate PiuA-PlyD4 against Streptococcus pneumoniae. Drug Des Devel Ther. 2023. https:\/\/doi.org\/10.2147\/dddt.S441302.","journal-title":"Drug Des Devel Ther"},{"key":"5751_CR59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009617","volume":"17","author":"H Bessaiah","year":"2021","unstructured":"Bessaiah H, et al. The RyfA small RNA regulates oxidative and osmotic stress responses and virulence in uropathogenic Escherichia coli. PLoS Pathog. 2021;17:e1009617. https:\/\/doi.org\/10.1371\/journal.ppat.1009617.","journal-title":"PLoS Pathog"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-026-05751-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-026-05751-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-026-05751-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:18:57Z","timestamp":1792541937000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-026-05751-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5751"],"URL":"https:\/\/doi.org\/10.1186\/s12917-026-05751-x","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"1 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments in this study were conducted under the guidelines of the Jilin University Institutional Animal Care and Use Committee and approved by the Animal Ethics Committee of Jilin University (Number of permit: SY202509021).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"617"}}