{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:45:20Z","timestamp":1790210720064,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["88887.601281\/2021-00"],"award-info":[{"award-number":["88887.601281\/2021-00"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["2023\/10579-8"],"award-info":[{"award-number":["2023\/10579-8"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["88887.601281\/2021-00"],"award-info":[{"award-number":["88887.601281\/2021-00"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2023\/10579-8"],"award-info":[{"award-number":["2023\/10579-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality, which are worsened by the increase in multidrug-resistant strains. New therapeutic\/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location, conservation among clinical isolates and adjuvant properties make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of type 1 and 3 fimbriae subunits in a murine model of K. pneumoniae lung infection. Methods: MrkA and FimA were produced as recombinant proteins in E. coli, purified and used to immunize mice subcutaneously. The immune responses were characterized and protection against pneumonia was evaluated after intranasal challenge. Results: Subcutaneous immunization with recombinant FimA and MrkA induced high IgG1 production; the antibodies efficiently recognized the native proteins at the bacterial surface, promoted C3 deposition and reduced biofilm formation by K. pneumoniae in vitro. Mice vaccinated with the co-administered proteins reduced the bacterial loads in the lungs after intranasal challenge, less inflammation and reduced tissue damage. Conclusion: The results suggest that both type 1 and type 3 fimbriae contribute to protection against K. pneumoniae lung infection, inducing antibodies that bind to the bacteria and favoring Complement deposition and clearance by the host, while inhibiting biofilm formation.<\/jats:p>","DOI":"10.3390\/vaccines13030303","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:39:03Z","timestamp":1741711143000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Protection Against Pneumonia Induced by Vaccination with Fimbriae Subunits from Klebsiella pneumoniae"],"prefix":"10.3390","volume":"13","author":[{"given":"Lucas","family":"Assoni","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Ciaparin","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monalisa Martins","family":"Trentini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Desenvolvimento de Vacinas, Instituto Butantan, S\u00e3o Paulo 05508-040, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4363-270X","authenticated-orcid":false,"given":"Juliana","family":"Baboghlian","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Vieira","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Aires","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es M\u00e9dicas, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-427X","authenticated-orcid":false,"given":"Carlos","family":"Martinez","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00f5es M\u00e9dicas, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-3215","authenticated-orcid":false,"given":"Lucio","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-0651","authenticated-orcid":false,"given":"Raquel","family":"Girardello","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8766-0452","authenticated-orcid":false,"given":"Lucas Miguel","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia de Sistemas e \u00d4micas em Ci\u00eancias da Sa\u00fade (LaBSOmiCS), Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-6009","authenticated-orcid":false,"given":"Anders P.","family":"Hakansson","sequence":"additional","affiliation":[{"name":"Division of Experimental Infection Medicine, Department of Translational Medicine, Lund University, 222 42 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-4541","authenticated-orcid":false,"given":"Thiago Rojas","family":"Converso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-3435","authenticated-orcid":false,"given":"Michelle","family":"Darrieux","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia Molecular e Cl\u00ednica, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024). Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Martin, R.M., and Bachman, M.A. (2018). Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00004"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tan, Y.H., Arros, P., Berrios-Pasten, C., Wijaya, I., Chu, W.H.W., Chen, Y., Cheam, G., Mohamed Naim, A.N., Marcoleta, A.E., and Ravikrishnan, A. (2024). Hypervirulent Klebsiella pneumoniae employs genomic island encoded toxins against bacterial competitors in the gut. ISME J., 18.","DOI":"10.1093\/ismejo\/wrae054"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/CMR.00001-19","article-title":"Hypervirulent Klebsiella pneumoniae","volume":"32","author":"Russo","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xu, L., Sun, X., and Ma, X. (2017). Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann. Clin. Microbiol. Antimicrob., 16.","DOI":"10.1186\/s12941-017-0191-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care-associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.2147\/IDR.S371248","article-title":"Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics","volume":"15","author":"Ramadan","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijid.2014.05.030","article-title":"Disease burden of intensive care unit-acquired pneumonia in China: A systematic review and meta-analysis","volume":"29","author":"Zhang","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S1473-3099(17)30747-8","article-title":"Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): A randomised, double-blind, phase 3 non-inferiority trial","volume":"18","author":"Torres","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, I.R., Lin, S.N., Wu, X.N., Chou, S.H., Wang, F.D., and Lin, Y.T. (2022). Clinical and Microbiological Characteristics of Bacteremic Pneumonia Caused by Klebsiella pneumoniae. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.903682"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13756-019-0660-x","article-title":"Clinical characteristics of patients with pneumonia caused by Klebsiella pneumoniae in Taiwan and prevalence of antimicrobial-resistant and hypervirulent strains: A retrospective study","volume":"9","author":"Juan","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nicolo, S., Mattiuz, G., Antonelli, A., Arena, F., Di Pilato, V., Giani, T., Baccani, I., Clemente, A.M., Castronovo, G., and Tanturli, M. (2022). Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect T(H)1\/T(H)17 Response. Microorganisms, 10.","DOI":"10.3390\/microorganisms10020384"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1080\/21505594.2021.1960101","article-title":"The hypermucoviscosity of hypervirulent K. pneumoniae confers the ability to evade neutrophil-mediated phagocytosis","volume":"12","author":"Xu","year":"2021","journal-title":"Virulence"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1007\/s40121-021-00533-4","article-title":"Current Stage in the Development of Klebsiella pneumoniae Vaccines","volume":"10","author":"Assoni","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Motamed, H., Yari, F., Javadirad, E., Golmohammadi, S., Alimoradi, S., Naleini, R., Chegene Lorestani, R., Nemati Zargaran, F., and Rostamian, M. (2024). Human vaccine candidates for infections caused by Klebsiella pneumoniae: A systematic review. Health Sci. Rep., 7.","DOI":"10.1002\/hsr2.70061"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Li, Y., and Ni, M. (2023). Regulation of biofilm formation in Klebsiella pneumoniae. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1238482"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: Going on the Offense with a Strong Defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1128\/IAI.00494-08","article-title":"Characterization of Klebsiella pneumoniae type 1 fimbriae by detection of phase variation during colonization and infection and impact on virulence","volume":"76","author":"Struve","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pacheco, T., Gomes, A.E.I., Siqueira, N.M.G., Assoni, L., Darrieux, M., Venter, H., and Ferraz, L.F.C. (2021). SdiA, a Quorum-Sensing Regulator, Suppresses Fimbriae Expression, Biofilm Formation, and Quorum-Sensing Signaling Molecules Production in Klebsiella pneumoniae. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.597735"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1590\/S0100-879X2004000800001","article-title":"A high-copy T7 Escherichia coli expression vector for the production of recombinant proteins with a minimal N-terminal His-tagged fusion peptide","volume":"37","author":"Ramos","year":"2004","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0009-9120(97)00049-0","article-title":"Removal of endotoxin from recombinant protein preparations","volume":"30","author":"Liu","year":"1997","journal-title":"Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4110\/in.2013.13.1.10","article-title":"Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype","volume":"13","author":"Jin","year":"2013","journal-title":"Immune Netw."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.02059-20","article-title":"The Role of IgG Subclass in Antibody-Mediated Protection against Carbapenem-Resistant Klebsiella pneumoniae","volume":"11","author":"Motley","year":"2020","journal-title":"mBio"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lopatto, E.D.B., Pinkner, J.S., Sanick, D.A., Potter, R.F., Liu, L.X., Baz\u00e1n Villica\u00f1a, J., Tamadonfar, K.O., Ye, Y., Zimmerman, M.I., and Gualberto, N.C. (2024). Conformational ensembles in Klebsiella pneumoniae FimH impact uropathogenesis. Proc. Natl. Acad. Sci. USA, 121.","DOI":"10.1073\/pnas.2409655121"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1128\/JB.00985-13","article-title":"Type 1 fimbriae contribute to catheter-associated urinary tract infections caused by Escherichia coli","volume":"196","author":"Reisner","year":"2014","journal-title":"J Bacteriol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijmm.2005.04.001","article-title":"Klebsiella pneumoniae type 3 fimbria-mediated immunity to infection in the murine model of respiratory disease","volume":"295","author":"Lavender","year":"2005","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1093\/infdis\/jiw021","article-title":"Target-Agnostic Identification of Functional Monoclonal Antibodies Against Klebsiella pneumoniae Multimeric MrkA Fimbrial Subunit","volume":"213","author":"Wang","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, Q., Chen, Y., Cvitkovic, R., Pennini, M.E., Chang, C.S., Pelletier, M., Bonnell, J., Koksal, A.C., Wu, H., and Dall'Acqua, W.F. (2017). Anti-MrkA Monoclonal Antibodies Reveal Distinct Structural and Antigenic Features of MrkA. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170529"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Berry, S.K., Rust, S., Irving, L., Bartholdson Scott, J., Weinert, L.A., Dougan, G., Christie, G., Warrener, P., Minter, R., and Grant, A.J. (2024). Characterization of mAbs against Klebsiella pneumoniae type 3 fimbriae isolated in a target-independent phage display campaign. Microbiol. Spectr., 12.","DOI":"10.1128\/spectrum.00400-24"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.micpath.2008.11.006","article-title":"Klebsiella pneumoniae MrkD adhesin-mediated immunity to respiratory infection and mapping the antigenic epitope by phage display library","volume":"46","author":"Li","year":"2009","journal-title":"Microb. Pathog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.micpath.2010.03.009","article-title":"Identification and characterization of Th cell epitopes in MrkD adhesin of Klebsiella pneumoniae","volume":"49","author":"Li","year":"2010","journal-title":"Microb. Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126217","DOI":"10.1016\/j.vaccine.2024.126217","article-title":"Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia","volume":"42","author":"Chen","year":"2024","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1128\/CVI.00620-15","article-title":"Potent In Vitro and In Vivo Activity of Plantibody Specific for Porphyromonas gingivalis FimA","volume":"23","author":"Choi","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1348-0421.2011.00305.x","article-title":"Cloning and characterization of heavy and light chain genes encoding the FimA-specific monoclonal antibodies that inhibit Porphyromonas gingivalis adhesion","volume":"55","author":"Koh","year":"2011","journal-title":"Microbiol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4110\/in.2009.9.5.203","article-title":"Production of Monoclonal Antibodies Specific to FimA of Porphyromonas gingivalis and Their Inhibitory Activity on Bacterial Binding","volume":"9","author":"Koh","year":"2009","journal-title":"Immune Netw."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1016\/j.vaccine.2020.06.052","article-title":"Type I pili, CsuA\/B and FimA induce a protective immune response against Acinetobacter baumannii","volume":"38","author":"Ramezanalizadeh","year":"2020","journal-title":"Vaccine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.fsi.2013.06.021","article-title":"The major fimbrial subunit protein of Edwardsiella tarda: Vaccine potential, adjuvant effect, and involvement in host infection","volume":"35","author":"Wang","year":"2013","journal-title":"Fish. Shellfish. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.molimm.2021.05.005","article-title":"Recombinant FimH, a fimbrial tip adhesin of Vibrio parahaemolyticus, elicits mixed T helper cell response and confers protection against Vibrio parahaemolyticus challenge in murine model","volume":"135","author":"Karan","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.archoralbio.2019.02.009","article-title":"FimH as a mucosal adjuvant enhances persistent antibody response and protective efficacy of the anti-caries vaccine","volume":"101","author":"Liu","year":"2019","journal-title":"Arch. Oral. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.antiviral.2017.01.020","article-title":"Incorporation of a bi-functional protein FimH enhances the immunoprotection of chitosan-pVP1 vaccine against coxsackievirus B3-induced myocarditis","volume":"140","author":"Fan","year":"2017","journal-title":"Antiviral Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: Differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Assoni, L., Couto, A.J.M., Vieira, B., Milani, B., Lima, A.S., Converso, T.R., and Darrieux, M. (2024). Animal models of Klebsiella pneumoniae mucosal infections. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1367422"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/3\/303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:50:54Z","timestamp":1760028654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/3\/303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["vaccines13030303"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13030303","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]}}}