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the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob\/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine\u2032s safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients.<\/jats:p>","DOI":"10.3390\/ijms251910379","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T09:46:20Z","timestamp":1727343980000},"page":"10379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Diabetic Mice Spleen Vulnerability Contributes to Decreased Persistence of Antibody Production after SARS-CoV-2 Vaccine"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-7268","authenticated-orcid":false,"given":"Yara","family":"Atef","sequence":"first","affiliation":[{"name":"Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1858-6009","authenticated-orcid":false,"given":"Tomoya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9402-924X","authenticated-orcid":false,"given":"Akitsu","family":"Masuda","sequence":"additional","affiliation":[{"name":"Laboratory of Creative Science for Insect Industries, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-911X","authenticated-orcid":false,"given":"Yuri","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-3994","authenticated-orcid":false,"given":"Akiyuki","family":"Nishimura","sequence":"additional","affiliation":[{"name":"National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), Okazaki 444-8787, Japan"},{"name":"Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences (NINS), Okazaki 444-8787, Japan"},{"name":"Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2527-3526","authenticated-orcid":false,"given":"Yasunari","family":"Kanda","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, National Institute of Health Sciences, Kawasaki 210-9501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kunisawa","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan"},{"name":"Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kusakabe","sequence":"additional","affiliation":[{"name":"Laboratory of Insect Genome Science, Kyushu University Graduate School of Bioresource and Bioenvironmental Sciences, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan"},{"name":"National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), Okazaki 444-8787, Japan"},{"name":"Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences (NINS), Okazaki 444-8787, Japan"},{"name":"Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref_1","unstructured":"Stierman, B., Afful, J., Carroll, M.D., Chen, T.C., Davy, O., Fink, S., Fryar, C.D., Gu, Q., Hales, C.M., and Hughes, J.P. (2021). National Health and Nutrition Examination Survey 2017\u2013March 2020 Prepandemic Data Files Development of Files and Prevalence Estimates for Selected Health Outcomes. National Health Statistics Reports, The Centers for Disease Control and Prevention (CDC)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S2213-8587(15)00379-4","article-title":"Diabetes and Infection: Assessing the Association with Glycaemic Control in Population-Based Studies","volume":"4","author":"Blundell","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.2337\/db20-0671","article-title":"Obesity and COVID-19 in Adult Patients with Diabetes","volume":"70","author":"Cao","year":"2021","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.2337\/dci21-0001","article-title":"Diabetes and COVID-19: Population Impact 18 Months into the Pandemic","volume":"44","author":"Gregg","year":"2021","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41586-020-2271-3","article-title":"Aerodynamic Analysis of SARS-CoV-2 in Two Wuhan Hospitals","volume":"582","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"563","DOI":"10.3906\/sag-2004-172","article-title":"Epidemiology of COVID-19","volume":"50","author":"Bulut","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/s41562-021-01122-8","article-title":"A global database of COVID-19 vaccinations","volume":"5","author":"Mathieu","year":"2020","journal-title":"Nat. Hum. Behav. Vol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rahmani, K., Shavaleh, R., Forouhi, M., Disfani, H.F., Kamandi, M., Oskooi, R.K., Foogerdi, M., Soltani, M., Rahchamani, M., and Mohaddespour, M. (2022). The Effectiveness of COVID-19 Vaccines in Reducing the Incidence, Hospitalization, and Mortality from COVID-19: A Systematic Review and Meta-Analysis. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.873596"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102406","DOI":"10.1016\/j.dsx.2022.102406","article-title":"Antibody Response Following SARS-CoV-2 Vaccination among Patients with Type 2 Diabetes Mellitus: A Systematic Review","volume":"16","author":"Soetedjo","year":"2022","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/s41467-022-30068-2","article-title":"Glycaemic Control Is Associated with SARS-CoV-2 Breakthrough Infections in Vaccinated Patients with Type 2 Diabetes","volume":"13","author":"Marfella","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e3465","DOI":"10.1002\/dmrr.3465","article-title":"Central Obesity, Smoking Habit, and Hypertension Are Associated with Lower Antibody Titres in Response to COVID-19 MRNA Vaccine","volume":"38","author":"Watanabe","year":"2022","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/s41591-023-02343-2","article-title":"Accelerated Waning of the Humoral Response to COVID-19 Vaccines in Obesity","volume":"29","author":"Horner","year":"2023","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e474","DOI":"10.1210\/clinem\/dgad001","article-title":"Prevaccination Glucose Time in Range Correlates with Antibody Response to SARS-CoV-2 Vaccine in Type 1 Diabetes","volume":"108","author":"Alhamar","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.2337\/db22-0053","article-title":"Immunogenicity and Safety of SARS-CoV-2 MRNA Vaccines in a Cohort of Patients with Type 1 Diabetes","volume":"71","author":"Sabiu","year":"2022","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liang, Z., Zhu, H., Wang, X., Jing, B., Li, Z., Xia, X., Sun, H., Yang, Y., Zhang, W., and Shi, L. (2020). Adjuvants for Coronavirus Vaccines. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.589833"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/cmi.2015.03","article-title":"Identification of an Ideal Adjuvant for Receptor-Binding Domain-Based Subunit Vaccines against Middle East Respiratory Syndrome Coronavirus","volume":"13","author":"Zhang","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41565-023-01404-4","article-title":"Nature Nanotechnology Adjuvant Lipidoid-Substituted Lipid Nanoparticles Augment the Immunogenicity of SARS-CoV-2 MRNA Vaccines","volume":"18","author":"Han","year":"2023","journal-title":"Nat. Nanotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Thuy, C., Le, T., Ahn, S.Y., Ho, T.L., Lee, J., Lee, D.-H., Hwang, H.S., Kang, S.-M., and Ko, E.-J. (2023). Adjuvant Effects of Combination Monophosphoryl Lipid A and Poly I:C on Antigen-Specific Immune Responses and Protective Efficacy of Influenza Vaccines. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-39210-6"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Suriano, F., Vieira-Silva, S., Falony, G., Roumain, M., Paquot, A., Pelicaen, R., R\u00e9gnier, M., Delzenne, N.M., Raes, J., and Muccioli, G.G. (2021). Novel Insights into the Genetically Obese (Ob\/Ob) and Diabetic (Db\/Db) Mice: Two Sides of the Same Coin. Microbiome, 9.","DOI":"10.1186\/s40168-021-01097-8"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kato, Y., Ariyoshi, K., Nohara, Y., Matsunaga, N., Shimauchi, T., Shindo, N., Nishimura, A., Mi, X., Kim, S.G., and Ide, T. (Br. J. Pharmacol., 2024). Inhibition of Dynamin-Related Protein 1-Filamin Interaction Improves Systemic Glucose Metabolism, Br. J. Pharmacol., early view.","DOI":"10.1111\/bph.16487"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1161\/CIRCRESAHA.121.317997","article-title":"COVID-19 and Cardiovascular Disease","volume":"128","author":"Chung","year":"2021","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1161\/CIRCULATIONAHA.121.056135","article-title":"Myocarditis with COVID-19 MRNA Vaccines","volume":"144","author":"Bozkurt","year":"2021","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1242\/dmm.001941","article-title":"Rodent Models of Diabetic Cardiomyopathy","volume":"2","author":"Bugger","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eaau6085","DOI":"10.1126\/sciimmunol.aau6085","article-title":"Structure and Function of the Immune System in the Spleen","volume":"4","author":"Lewis","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, N., Ji, Q., Liu, Z., Tang, K., Xie, Y., Li, K., Zhou, J., Li, S., Shang, H., and Shi, Z. (2022). Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant. Viruses, 14.","DOI":"10.3390\/v14030501"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s43094-020-00151-w","article-title":"Diabetes and Cardiovascular Disease: Inter-Relation of Risk Factors and Treatment","volume":"6","author":"Sharma","year":"2020","journal-title":"Future J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ssentongo, P., Zhang, Y., Witmer, L., Chinchilli, V.M., and Ba, D.M. (2022). Association of COVID-19 with Diabetes: A Systematic Review and Meta-Analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24185-7"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xiong, X., Lui, D.T.W., Chung, M.S.H., Au, I.C.H., Lai, F.T.T., Wan, E.Y.F., Chui, C.S.L., Li, X., Cheng, F.W.T., and Cheung, C.L. (2023). Incidence of Diabetes Following COVID-19 Vaccination and SARS-CoV-2 Infection in Hong Kong: A Population-Based Cohort Study. PLoS Med., 20.","DOI":"10.1371\/journal.pmed.1004274"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"416254","DOI":"10.1155\/2011\/416254","article-title":"Development of a Nongenetic Mouse Model of Type 2 Diabetes","volume":"2011","author":"Gilbert","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13098-022-00935-5","article-title":"Insight into the Hepatoprotective, Hypolipidemic, and Antidiabetic Impacts of Aliskiren in Streptozotocin-Induced Diabetic Liver Disease in Mice","volume":"14","author":"Mahfoz","year":"2022","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_32","first-page":"e36588","article-title":"Investigating the Impact of COVID-19 Vaccines on Liver Function: Insights from a Single-Institute Study","volume":"15","author":"Rammohan","year":"2023","journal-title":"Cureus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nri3795","article-title":"The Generation of Antibody-Secreting Plasma Cells","volume":"15","author":"Nutt","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.2337\/db11-0159","article-title":"Immunosuppressive Effects of Streptozotocin-Induced Diabetes Result in Absolute Lymphopenia and a Relative Increase of T Regulatory Cells","volume":"60","author":"Muller","year":"2011","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yang, Y., Qian, J., Li, B., Lu, M., Le, G., and Xie, Y. (2021). Metabolomics Based On1 H-Nmr Reveal the Regulatory Mechanisms of Dietary Methionine Restriction on Splenic Metabolic Dysfunction in Obese Mice. Foods, 10.","DOI":"10.3390\/foods10102439"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/rb\/rbu003","article-title":"Counting CD4+ and CD8+ T Cells in the Spleen: A Novel In Vivo Method for Assessing Biomaterial Immunotoxicity","volume":"1","author":"Shieh","year":"2014","journal-title":"Regen. Biomater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.bbrc.2016.01.096","article-title":"Postnatal Lethality and Abnormal Development of Foregut and Spleen in Ndrg4 Mutant Mice","volume":"470","author":"Qu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, H., Kim, M.J., Lee, I.K., Hong, C.W., and Jeon, J.H. (2024). Impact of Hyperglycemia on Immune Cell Function: A Comprehensive Review. Diabetology International, Springer.","DOI":"10.1007\/s13340-024-00741-6"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1574-695X.1999.tb01397.x","article-title":"Immune Dysfunction in Patients with Diabetes Mellitus (DM)","volume":"26","author":"Geerlings","year":"1999","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Alexander, M., Cho, E., Gliozheni, E., Salem, Y., Cheung, J., and Ichii, H. (2024). Pathology of Diabetes-Induced Immune Dysfunction. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137105"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.amjms.2015.11.011","article-title":"The Effect of Short-Term Hyperglycemia on the Innate Immune System","volume":"351","author":"Jafar","year":"2016","journal-title":"Am. J. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Masuda, A., Lee, J.M., Miyata, T., Mon, H., Sato, K., Oyama, K., Sakurai, Y., Yasuda, J., Takahashi, D., and Ueda, T. (2022). Optimization of SARS-CoV-2 Spike Protein Expression in the Silkworm and Induction of Efficient Protective Immunity by Inoculation with Alum Adjuvants. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.803647"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:04:06Z","timestamp":1760112246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":42,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910379"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910379","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}