Obesity is a growing global health concern with profound effects on immune function and vaccine efficacy. This study investigated the impact of obesity on immune responses to tick-borne encephalitis virus (TBEV) vaccination and infection using a mouse model. Mice on a high-fat diet (HFD) exhibited increased body weight, fat mass and a pre-diabetic state compared to standard chow diet (SCD) controls. After vaccination with the TBEV vaccine (Encepur), HFD mice showed significantly lower TBEV-specific IgG litres and neutralizing antibody levels compared to SCD mice. Splenocyte counts per organ mass were significantly higher in vaccinated SCD mice compared to their HFD counterparts, correlating with the elevated IgG litres observed in the SCD group. These results underscore the critical role of diet in shaping the immune response and vaccine efficacy. Following TBEV infection, HFD mice did not display increased disease severity or elevated viral litres in the serum, spleen or brain relative to SCD controls, indicating that obesity did not exacerbate viral replication or dissemination. However, a sex-dependent effect of obesity on the humoral immune response was observed. Male HFD mice produced antibody litres comparable to their SCD counterparts, suggesting minimal impact of obesity on their immune response. In contrast, female HFD mice exhibited significant impairments in TBEV-specific IgG and neutralizing antibody production compared to female SCD mice, as well as both male HFD and male SCD groups. These findings highlight a complex interplay between obesity, sex and immune function, with obesity disproportionately impairing the immune response after TBEV vaccination and infection.

Czech Centre for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences Vestec Czechia

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Ceske Budejovice Czechia

Veterinary Research Institute Brno Czechia

Zobrazit více v PubMed

Alfaris N, Alqahtani AM, Alamuddin N, Rigas G. Global Impact of Obesity. Gastroenterol Clin North Am. 2023;52:277–293. doi: 10.1016/j.gtc.2023.03.002. PubMed DOI

Marques A, Peralta M, Naia A, Loureiro N, de Matos MG. Prevalence of adult overweight and obesity in 20 European countries, 2014. Eur J Public Health. 2018;28:295–300. doi: 10.1093/eurpub/ckx143. PubMed DOI

Karlsson EA, Beck MA. The burden of obesity on infectious disease. Exp Biol Med. 2010;235:1412–1424. doi: 10.1258/ebm.2010.010227. DOI

Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res. 2002;10 Suppl 2:97S–104S. doi: 10.1038/oby.2002.202. PubMed DOI

Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009;121:21–33. doi: 10.3810/pgm.2009.11.2074. PubMed DOI PMC

James WP. What are the health risks? The medical consequences of obesity and its health risks. Exp Clin Endocrinol Diabetes. 1998;106 Suppl 2:1–6. doi: 10.1055/s-0029-1212028. DOI

Jiang Z, Tabuchi C, Gayer SG, Bapat SP. Immune dysregulation in obesity. Annu Rev Pathol. 2025;20:483–509. doi: 10.1146/annurev-pathmechdis-051222-015350. PubMed DOI

Chiffi G, Grandgirard D, Leib SL, Chrdle A, Růžek D. Tick-borne encephalitis: a comprehensive review of the epidemiology, virology, and clinical picture. Rev Med Virol. 2023;33:e2470. doi: 10.1002/rmv.2470. PubMed DOI

Ruzek D, Avšič Županc T, Borde J, Chrdle A, Eyer L, et al. Tick-borne encephalitis in Europe and Russia: review of pathogenesis, clinical features, therapy, and vaccines. Antiviral Res. 2019;164:23–51. doi: 10.1016/j.antiviral.2019.01.014. PubMed DOI

Amicizia D, Domnich A, Panatto D, Lai PL, Cristina ML, et al. Epidemiology of tick-borne encephalitis (TBE) in Europe and its prevention by available vaccines. Hum Vaccin Immunother. 2013;9:1163–1171. doi: 10.4161/hv.23802. PubMed DOI PMC

Bogovic P, Lotric-Furlan S, Strle F. What tick-borne encephalitis may look like: clinical signs and symptoms. Travel Med Infect Dis. 2010;8:246–250. doi: 10.1016/j.tmaid.2010.05.011. PubMed DOI

Bogovic P, Strle F. Tick-borne encephalitis: a review of epidemiology, clinical characteristics, and management. World J Clin Cases. 2015;3:430–441. doi: 10.12998/wjcc.v3.i5.430. PubMed DOI PMC

Kollaritsch H, Paulke-Korinek M, Holzmann H, Hombach J, Bjorvatn B, et al. Vaccines and vaccination against tick-borne encephalitis. Expert Rev Vaccines. 2012;11:1103–1119. doi: 10.1586/erv.12.86. PubMed DOI

Garner-Spitzer E, Poellabauer E-M, Wagner A, Guzek A, Zwazl I, et al. Obesity and sex affect the immune responses to tick-borne encephalitis booster vaccination. Front Immunol. 2020;11:860. doi: 10.3389/fimmu.2020.00860. PubMed DOI PMC

Chauvin C, Retnakumar SV, Bayry J. Obesity negatively impacts maintenance of antibody response to COVID-19 vaccines. Cell Rep Med . 2023;4:101117. doi: 10.1016/j.xcrm.2023.101117. PubMed DOI PMC

Ou X, Jiang J, Lin B, Liu Q, Lin W, et al. Antibody responses to COVID-19 vaccination in people with obesity: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2023;17:e13078. doi: 10.1111/irv.13078. DOI

Nasr M-JC, Geerling E, Pinto AK. Impact of obesity on vaccination to SARS-CoV-2. Front Endocrinol. 2022;13:898810. doi: 10.3389/fendo.2022.898810. DOI

Abd Alhadi M, Friedman LM, Karlsson EA, Cohen-Lavi L, Burkovitz A, et al. Obesity Is associated with an impaired baseline repertoire of anti-influenza virus antibodies. Microbiol Spectr. 2023;11:e0001023. doi: 10.1128/spectrum.00010-23. PubMed DOI PMC

Kristinsdottir I, Haraldsson A, Brynjolfsson SF, Helgason T, Ludviksson BR, et al. Obesity in adolescents does not influence early immune responses to influenza vaccination. Infect Dis (Lond) 2023;55:415–424. doi: 10.1080/23744235.2023.2195491. PubMed DOI

Cho W-J, Lee D-K, Lee S-Y, Sohn S-H, Park H-L, et al. Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function. Acta Virol. 2016;60:298–306. doi: 10.4149/av_2016_03_298. PubMed DOI

Park H-L, Shim S-H, Lee E-Y, Cho W, Park S, et al. Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine. Hum Vaccin Immunother. 2014;10:1181–1186. doi: 10.4161/hv.28332. PubMed DOI PMC

Young KM, Gray CM, Bekker LG. Is obesity a risk factor for vaccine non-responsiveness? PLoS One. 2013;8:e82779. doi: 10.1371/journal.pone.0082779. PubMed DOI PMC

Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA. 1985;254:3187–3189. PubMed

Weber DJ, Rutala WA, Samsa GP, Bradshaw SE, Lemon SM. Impaired immunogenicity of hepatitis B vaccine in obese persons. N Engl J Med. 1986;314:1393. doi: 10.1056/NEJM198605223142120. PubMed DOI

Hameed M, Geerling E, Pinto AK, Miraj I, Weger-Lucarelli J. Immune response to arbovirus infection in obesity. Front Immunol. 2022;13:968582. doi: 10.3389/fimmu.2022.968582. PubMed DOI PMC

Schwarz NG, Girmann M, Randriamampionona N, Bialonski A, Maus D, et al. Seroprevalence of antibodies against Chikungunya, Dengue, and Rift Valley fever viruses after febrile illness outbreak, Madagascar. Emerg Infect Dis. 2012;18:1780–1786. doi: 10.3201/eid1811.111036. PubMed DOI PMC

Gérardin P, Guernier V, Perrau J, Fianu A, Le Roux K, et al. Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. BMC Infect Dis. 2008;8:99. doi: 10.1186/1471-2334-8-99. PubMed DOI PMC

Padmakumar B, Jayan JB, Menon R, Kottarathara AJ. Clinical profile of chikungunya sequelae, association with obesity and rest during acute phase. Southeast Asian J Trop Med Public Health. 2010;41:85–91. PubMed

Kalayanarooj S, Nimmannitya S. Is dengue severity related to nutritional status? Southeast Asian J Trop Med Public Health. 2005;36:378–384. PubMed

Ahlm C, Eliasson M, Vapalahti O, Evander M. Seroprevalence of Sindbis virus and associated risk factors in northern Sweden. Epidemiol Infect. 2014;142:1559–1565. doi: 10.1017/S0950268813002239. PubMed DOI PMC

Calamusa G, Valenti RM, Vitale F, Mammina C, Romano N, et al. Seroprevalence of and risk factors for Toscana and Sicilian virus infection in a sample population of Sicily (Italy) J Infect. 2012;64:212–217. doi: 10.1016/j.jinf.2011.11.012. PubMed DOI PMC

Kozuch O, Mayer V. Pig kidney epithelial (PS) cells: a perfect tool for the study of flaviviruses and some other arboviruses. Acta Virol. 1975;19:498. PubMed

Salat J, Strakova P, Ruzek D. Dynamics of whole virus and non-structural protein 1 (NS1) IgG response in mice immunized with two commercial tick-borne encephalitis vaccines. Vaccines. 2022;10:1001. doi: 10.3390/vaccines10071001. PubMed DOI PMC

Eyer L, Svoboda P, Palus M, Salat J, Růžek D. Methods for evaluation of antivirals and neutralizing antibodies against tick-borne encephalitis virus. Methods Mol Biol. 2025;2936:125–136. doi: 10.1007/978-1-0716-4587-1_14. PubMed DOI

Belosludtsev KN, Starinets VS, Belosludtsev MN, Mikheeva IB, Dubinin MV, et al. Chronic treatment with dapagliflozin protects against mitochondrial dysfunction in the liver of C57BL/6NCrl mice with high-fat diet/streptozotocin-induced diabetes mellitus. Mitochondrion. 2021;59:246–254. doi: 10.1016/j.mito.2021.06.008. PubMed DOI

Smoczek M, Vital M, Wedekind D, Basic M, Zschemisch N-H, et al. A combination of genetics and microbiota influences the severity of the obesity phenotype in diet-induced obesity. Sci Rep. 2020;10:6118. doi: 10.1038/s41598-020-63340-w. PubMed DOI PMC

van der Heijden RA, Sheedfar F, Morrison MC, Hommelberg PP, Kor D, et al. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging. 2015;7:256–268. doi: 10.18632/aging.100738. PubMed DOI PMC

Chu DT, Malinowska E, Jura M, Kozak LP. C57BL/6J mice as a polygenic developmental model of diet-induced obesity. Physiol Rep. 2017;5:e13093. doi: 10.14814/phy2.13093. PubMed DOI PMC

Agudelo M, Palus M, Keeffe JR, Bianchini F, Svoboda P, et al. Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease. J Exp Med. 2021;218:e20210236. doi: 10.1084/jem.20210236. PubMed DOI PMC

Weger-Lucarelli J, Carrau L, Levi LI, Rezelj V, Vallet T, et al. Host nutritional status affects alphavirus virulence, transmission, and evolution. PLoS Pathog. 2019;15:e1008089. doi: 10.1371/journal.ppat.1008089. PubMed DOI PMC

Suyama S, Boxall S, Grace B, Fořtová A, Pychova M, et al. Changes in metabolite profiles in the cerebrospinal fluid and in human neuronal cells upon tick-borne encephalitis virus infection. J Neuroinflammation. 2025;22:157. doi: 10.1186/s12974-025-03478-4. PubMed DOI PMC

Geerling E, Stone ET, Steffen TL, Hassert M, Brien JD, et al. Obesity enhances disease severity in female mice following west nile virus infection. Front Immunol. 2021;12:739025. doi: 10.3389/fimmu.2021.739025. PubMed DOI PMC

Chuong C, Bates TA, Akter S, Werre SR, LeRoith T, et al. Nutritional status impacts dengue virus infection in mice. BMC Biol. 2020;18:106. doi: 10.1186/s12915-020-00828-x. PubMed DOI PMC

Varghese M, Griffin C, Abrishami S, Eter L, Lanzetta N, et al. Sex hormones regulate metainflammation in diet-induced obesity in mice. J Biol Chem. 2021;297:101229. doi: 10.1016/j.jbc.2021.101229. PubMed DOI PMC

Růzek D, Salát J, Palus M, Gritsun TS, Gould EA, et al. CD8+ T-cells mediate immunopathology in tick-borne encephalitis. Virology. 2009;384:1–6. doi: 10.1016/j.virol.2008.11.023. PubMed DOI

Pokorna Formanova P, Palus M, Salat J, Hönig V, Stefanik M, et al. Changes in cytokine and chemokine profiles in mouse serum and brain, and in human neural cells, upon tick-borne encephalitis virus infection. J Neuroinflammation. 2019;16:205. doi: 10.1186/s12974-019-1596-z. PubMed DOI PMC

Gervais A, Marchal A, Fortova A, Berankova M, Krbkova L, et al. Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients. J Exp Med. 2024;221:e20240637. doi: 10.1084/jem.20240637. PubMed DOI PMC

Chotiwan N, Rosendal E, Willekens SMA, Schexnaydre E, Nilsson E, et al. Type I interferon shapes brain distribution and tropism of tick-borne flavivirus. Nat Commun. 2023;14:2007. doi: 10.1038/s41467-023-37698-0. PubMed DOI PMC

Berankova M, Holoubek J, Hönig V, Matusova Z, Palus M, et al. Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain. J Neuroinflammation. 2025;22:22. doi: 10.1186/s12974-025-03354-1. PubMed DOI PMC

Palus M, Sohrabi Y, Broman KW, Strnad H, Šíma M, et al. A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus. BMC Neurosci. 2018;19:39. doi: 10.1186/s12868-018-0438-8. PubMed DOI PMC

Palus M, Vojtíšková J, Salát J, Kopecký J, Grubhoffer L, et al. Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system. J Neuroinflammation. 2013;10:77. doi: 10.1186/1742-2094-10-77. PubMed DOI PMC

Perlman RL. Mouse models of human disease: an evolutionary perspective. Evol Med Public Health. 2016;2016:170–176. doi: 10.1093/emph/eow014. PubMed DOI PMC