{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T22:55:15Z","timestamp":1782168915420,"version":"3.54.5"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danmarks Innovationsfond","award":["8053-00175B"],"award-info":[{"award-number":["8053-00175B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Hypersensitivity to a contact allergen is one of the most abundant forms of inflammatory skin disease. Today, more than 20% of the general population are sensitized to one or more contact allergens, making this disease an important healthcare issue, as re-exposure to the allergen can initiate the clinical disease termed allergic contact dermatitis (ACD). The current standard treatment using corticosteroids is effective, but it has side effects when used for longer periods. Therefore, there is a need for new alternative therapies for severe ACD. In this study, we used the versatile Tag\/Catcher AP205 capsid virus-like particle (cVLP) vaccine platform to develop an IL-1\u03b2-targeted vaccine and to assess the immunogenicity and in vivo efficacy of the vaccine in a translational mouse model of ACD. We show that vaccination with cVLPs displaying full-length murine IL-1\u03b2 elicits high titers of neutralizing antibodies, leading to a significant reduction in local IL-1\u03b2 levels as well as clinical symptoms induced by treatment with 1-Fluoro-2,4-dinitrobenzene (DNFB). Moreover, we show that a single amino acid mutation in muIL-1\u03b2 reduces the biological activity while maintaining the ability to induce neutralizing antibodies. Collectively, the data suggest that a cVLP-based vaccine displaying full-length IL-1\u03b2 represents a promising vaccine candidate for use as an alternative treatment modality against severe ACD.<\/jats:p>","DOI":"10.3390\/vaccines10050828","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T05:12:27Z","timestamp":1653455547000},"page":"828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preclinical Efficacy of a Capsid Virus-like Particle-Based Vaccine Targeting IL-1\u03b2 for Treatment of Allergic Contact Dermatitis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-9857","authenticated-orcid":false,"given":"Louise","family":"Goks\u00f8yr","sequence":"first","affiliation":[{"name":"Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"AdaptVac Aps, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-3884","authenticated-orcid":false,"given":"Anders B.","family":"Funch","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Okholm","sequence":"additional","affiliation":[{"name":"Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor G.","family":"Theander","sequence":"additional","affiliation":[{"name":"Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem Adriaan","family":"de Jongh","sequence":"additional","affiliation":[{"name":"AdaptVac Aps, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Bonefeld","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-7830","authenticated-orcid":false,"given":"Adam F.","family":"Sander","sequence":"additional","affiliation":[{"name":"Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"AdaptVac Aps, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/cod.13119","article-title":"Prevalence of contact allergy in the general population: A systematic review and meta-analysis","volume":"80","author":"Alinaghi","year":"2019","journal-title":"Contact Dermatitis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/bjd.14167","article-title":"Prevalence of contact allergy in the general population in different European regions","volume":"174","author":"Diepgen","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Uter, W., Werfel, T., White, I.R., and Johansen, J.D. (2018). Contact allergy: A review of current problems from a clinical perspective. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15061108"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1600-0536.2007.01220.x","article-title":"The epidemiology of contact allergy in the general population--prevalence and main findings","volume":"57","author":"Thyssen","year":"2007","journal-title":"Contact Dermatitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1021\/tx7002239","article-title":"Allergic contact dermatitis\u2014Formation, structural requirements, and reactivity of skin sensitizers","volume":"21","author":"Karlberg","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1365-2133.2007.08162.x","article-title":"The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans","volume":"157","author":"Friedmann","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/j.1398-9995.2011.02652.x","article-title":"Mechanisms of chemical-induced innate immunity in allergic contact dermatitis","volume":"66","author":"Martin","year":"2011","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/cod.13327","article-title":"Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment","volume":"81","author":"Thyssen","year":"2019","journal-title":"Contact Dermatitis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12016-018-8705-0","article-title":"Contact Dermatitis to Medications and Skin Products","volume":"56","author":"Nguyen","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/sj.jid.5700819","article-title":"Activation of the IL-1\u03b2-processing inflammasome is involved in contact hypersensitivity","volume":"127","author":"Watanabe","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/cod.12270","article-title":"Epicutaneous exposure to nickel induces nickel allergy in mice via a MyD88-dependent and interleukin-1-dependent pathway","volume":"71","author":"Vennegaard","year":"2014","journal-title":"Contact Dermatitis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/cod.13955","article-title":"The role of interleukin-1\u03b2 in the immune response to contact allergens","volume":"85","author":"Yeung","year":"2021","journal-title":"Contact Dermatitis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1073\/pnas.89.4.1398","article-title":"Early molecular events in the induction phase of contact sensitivity","volume":"89","author":"Enk","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0300-483X(99)00145-6","article-title":"Epidermal cytokines in experimental contact dermatitis","volume":"142","author":"Corsini","year":"2000","journal-title":"Toxicology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.4049\/jimmunol.150.9.3698","article-title":"An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin","volume":"150","author":"Enk","year":"1993","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00296-011-2096-3","article-title":"Injection-site reactions upon Kineret (anakinra) administration: Experiences and explanations","volume":"32","author":"Kaiser","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1001\/jama.2011.406","article-title":"Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up","volume":"305","author":"Bartelds","year":"2011","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1586\/14760584.2016.1159136","article-title":"Frietze Moving Towards a New Class of Vaccines for Non- infectious Chronic Diseases","volume":"15","author":"Chackerian","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1080\/19420862.2015.1081323","article-title":"The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1\u03b2","volume":"7","author":"Rondeau","year":"2015","journal-title":"MAbs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R34","DOI":"10.1186\/ar3266","article-title":"Canakinumab (ACZ885, a fully human IgG1 anti-IL-1\u03b2 mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS)","volume":"13","author":"Ramos","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa0810787","article-title":"Use of canakinumab in the cryopyrin-associated periodic syndrome","volume":"360","author":"Lachmann","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrd1284","article-title":"Therapeutic vaccination for chronic diseases: A new class of drugs in sight","volume":"3","author":"Bachmann","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1073\/pnas.91.18.8532","article-title":"A vaccine that prevents pregnancy in women","volume":"91","author":"Talwar","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1126\/science.8248784","article-title":"The Influence of Antigen Organization on B Cell Responsiveness","volume":"262","author":"Bachmann","year":"1993","journal-title":"Science"},{"key":"ref_25","first-page":"3811","article-title":"Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines","volume":"7","author":"Leneghan","year":"2017","journal-title":"Nat. Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1002\/1521-4141(200211)32:11<3305::AID-IMMU3305>3.0.CO;2-J","article-title":"Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation","volume":"32","author":"Jegerlehner","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1016\/j.vaccine.2005.03.030","article-title":"Improvement of collagen-induced arthritis by active immunization against murine IL-1\u03b2 peptides designed by molecular modelling","volume":"23","author":"Capini","year":"2005","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/eji.200737989","article-title":"Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis","volume":"38","author":"Spohn","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14048","DOI":"10.1038\/mtm.2014.48","article-title":"Preclinical efficacy and safety of an anti-IL-1\u03b2 vaccine for the treatment of type 2 diabetes","volume":"1","author":"Spohn","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/mt.2015.227","article-title":"Development of an interleukin-1\u03b2 vaccine in patients with type 2 diabetes","volume":"24","author":"Timper","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12951-016-0181-1","article-title":"Bacterial superglue enables easy development of efficient virus-like particle based vaccines","volume":"14","author":"Thrane","year":"2016","journal-title":"J. Nanobiotechnology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1021\/acs.bioconjchem.7b00174","article-title":"Dual Plug-and-Display Synthetic Assembly Using Orthogonal Reactive Proteins for Twin Antigen Immunization","volume":"28","author":"Brune","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0022-1759(90)90029-U","article-title":"Removal of endotoxin from protein solutions by phase separation using Triton X-114","volume":"132","author":"Aida","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/all.14986","article-title":"CD8 + tissue-resident memory T cells recruit neutrophils that are essential for flare-ups in contact dermatitis","volume":"77","author":"Funch","year":"2022","journal-title":"Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6632","DOI":"10.1021\/bi00144a002","article-title":"Multiple Amino Acid Substitutions Suggest a Structural Basis for the Separation of Biological Activity and Receptor Binding in a Mutant Interleukin-1\/8 Protein1","volume":"31","author":"Auron","year":"1992","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/386190a0","article-title":"Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1\u03b2","volume":"386","author":"Vigers","year":"1997","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11477","DOI":"10.1074\/jbc.270.19.11477","article-title":"Mapping receptor binding sites in interleukin (IL)-1 receptor antagonist and IL-1\u03b2 by site-directed mutagenesis. Identification of a single site in IL-1ra and two sites in IL-1\u03b2","volume":"270","author":"Evans","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12874","DOI":"10.1016\/S0021-9258(18)99957-6","article-title":"X-ray Structure of Interleukin-1 Receptor Antagonist at 2.0-A Resolution","volume":"269","author":"Vigers","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.1016\/S0021-9258(19)39265-8","article-title":"A point mutation uncouples human interleukin-1? biological activity and receptor binding","volume":"265","author":"Gehrke","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1408749","DOI":"10.1080\/2162402X.2017.1408749","article-title":"Virus-like particle display of HER2 induces potent anti-cancer responses","volume":"7","author":"Palladini","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0140-6736(08)60381-5","article-title":"Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: A double-blind, randomised, placebo-controlled phase IIa study","volume":"371","author":"Tissot","year":"2008","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13195-015-0108-3","article-title":"Long-term treatment with active A\u03b2 immunotherapy with CAD106 in mild Alzheimer\u2019s disease","volume":"7","author":"Farlow","year":"2015","journal-title":"Alzheimers. Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.vaccine.2013.02.001","article-title":"Active immunotherapy for chronic diseases","volume":"31","author":"Bachmann","year":"2013","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41467-020-20251-8","article-title":"Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity","volume":"12","author":"Fougeroux","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.molmed.2020.01.007","article-title":"Vaccination against Allergy: A Paradigm Shift?","volume":"26","author":"Bachmann","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1084\/jem.20090199","article-title":"Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: A novel therapy for cat allergy","volume":"206","author":"Schmitz","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/all.13268","article-title":"Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells","volume":"73","author":"Engeroff","year":"2017","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/eji.201242687","article-title":"A VLP-based vaccine against interleukin-1\u03b1 protects mice from atherosclerosis","volume":"43","author":"Tissot","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.4049\/jimmunol.1000030","article-title":"A Virus-Like Particle-Based Anti-Nerve Growth Factor Vaccine Reduces Inflammatory Hyperalgesia: Potential Long-Term Therapy for Chronic Pain","volume":"186","author":"Zeilhofer","year":"2011","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/cod.12715","article-title":"Rapid allergen-induced interleukin-17 and interferon-\u03b3 secretion by skin-resident memory CD8 + T cells","volume":"76","author":"Schmidt","year":"2017","journal-title":"Contact Dermatitis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/art.10870","article-title":"Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial","volume":"48","author":"Fleischmann","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1136\/ard.2005.048371","article-title":"Safety of extended treatment with anakinra in patients with rheumatoid arthritis","volume":"65","author":"Fleischmann","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1128\/iai.62.2.457-461.1994","article-title":"Interleukin-1 is involved in mouse resistance to Mycobacterium avium","volume":"62","author":"Denis","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11008","DOI":"10.1073\/pnas.93.20.11008","article-title":"Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice","volume":"93","author":"Hirsch","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.4049\/jimmunol.159.5.2452","article-title":"Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice","volume":"159","author":"Labow","year":"1997","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1128\/IAI.67.4.1901-1909.1999","article-title":"Effects of Interleukin-1 Receptor Antagonist Overexpression on Infection by Listeria monocytogenes","volume":"67","author":"Irikura","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4049\/jimmunol.169.1.393","article-title":"The Epistatic Interrelationships of IL-1, IL-1 Receptor Antagonist, and the Type I IL-1 Receptor","volume":"169","author":"Irikura","year":"2002","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.vaccine.2010.10.045","article-title":"Blocking IL-1\u03b1 but not IL-1\u03b2 increases susceptibility to chronic Mycobacterium tuberculosis infection in mice","volume":"29","author":"Guler","year":"2011","journal-title":"Vaccine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/ni.1925","article-title":"Structural insights into the assembly and activation of IL-1b with its receptors","volume":"11","author":"Wang","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/pro.2441","article-title":"Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses","volume":"23","author":"Krumm","year":"2014","journal-title":"Protein Sci."},{"key":"ref_62","first-page":"6","article-title":"IL-1 Vaccination Is Suitable for Treating Inflammatory Diseases","volume":"8","author":"Oliviero","year":"2017","journal-title":"Front. Pharmacol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/5\/828\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:17:11Z","timestamp":1760138231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/5\/828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["vaccines10050828"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10050828","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]}}}