{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:01:12Z","timestamp":1781557272714,"version":"3.54.5"},"reference-count":128,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Influenza vaccines are designed to mimic natural influenza virus exposure and stimulate a long-lasting immune response to future infections. The evolving nature of the influenza virus makes vaccination an important and efficacious strategy to reduce healthcare-related complications of influenza. Several lines of evidence indicate that influenza vaccination may induce nonspecific effects, also referred to as heterologous or pleiotropic effects, that go beyond protection against infection. Different explanations are proposed, including the upregulation and downregulation of cytokines and epigenetic reprogramming in monocytes and natural killer cells, imprinting an immunological memory in the innate immune system, a phenomenon termed \u201ctrained immunity\u201d. Also, cross-reactivity between related stimuli and bystander activation, which entails activation of B and T lymphocytes without specific recognition of antigens, may play a role. In this review, we will discuss the possible nonspecific effects of influenza vaccination in cardiovascular disease, type 1 diabetes, cancer, and Alzheimer\u2019s disease, future research questions, and potential implications. A discussion of the potential effects on infections by other pathogens is beyond the scope of this review.<\/jats:p>","DOI":"10.3390\/vaccines11091419","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:25:33Z","timestamp":1692951933000},"page":"1419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pleiotropic Effects of Influenza Vaccination"],"prefix":"10.3390","volume":"11","author":[{"given":"Astrid Johannesson","family":"Hjelholt","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"},{"name":"Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergs Gade 10, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Pharmacology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bergh","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, \u00d6rebro University, S-701 82 \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, One Gustave L. Levi Place, P.O. Box 1030, New York, NY 10029-6574, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Fr\u00f6bert","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"},{"name":"Department of Clinical Pharmacology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health, Aarhus University, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"},{"name":"Faculty of Health, Department of Cardiology, \u00d6rebro University, SE-701 82 \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads Fuglsang","family":"Kjolby","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"},{"name":"Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergs Gade 10, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Pharmacology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A guide to vaccinology: From basic principles to new developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/cid\/cit209","article-title":"Heterologous (\u201cnonspecific\u201d) and sex-differential effects of vaccines: Epidemiology, clinical trials, and emerging immunologic mechanisms","volume":"57","author":"Flanagan","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.cmi.2019.08.011","article-title":"Developing the concept of beneficial non-specific effect of live vaccines with epidemiological studies","volume":"25","author":"Aaby","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Novakovic, B., Messina, N., and Curtis, L. (2018). The Heterologous Effects of Bacillus Calmette-Gu\u00e9rin (BCG) Vaccine and Trained Innate Immunity. The Value of BCG and TNF in Autoimmunity, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-12-814603-3.00006-9"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"i5170","DOI":"10.1136\/bmj.i5170","article-title":"Association of BCG, DTP, and measles containing vaccines with childhood mortality: Systematic review","volume":"355","author":"Higgins","year":"2016","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/ije\/dyr063","article-title":"Smallpox vaccination and all-cause infectious disease hospitalization: A Danish register-based cohort study","volume":"40","author":"Sorup","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev.me.28.020177.002421","article-title":"BCG as adjuvant immunotherapy for neoplasia","volume":"28","author":"Hersh","year":"1977","journal-title":"Annu. Rev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejca.2004.09.023","article-title":"Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients","volume":"41","author":"Kolmel","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1046\/j.1523-1747.2002.00643.x","article-title":"Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: Results of the FEBIM study","volume":"119","author":"Pfahlberg","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15986","DOI":"10.1038\/s41598-017-16067-0","article-title":"Early vaccination protects against childhood leukemia: A systematic review and meta-analysis","volume":"7","author":"Morra","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/archdischild-2013-305655","article-title":"Does neonatal BCG vaccination prevent allergic disease in later life?","volume":"99","author":"Freyne","year":"2014","journal-title":"Arch. Dis. Child."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/ije\/dyp307","article-title":"Does BCG vaccination protect against the development of childhood asthma? A systematic review and meta-analysis of epidemiological studies","volume":"39","author":"Parent","year":"2010","journal-title":"Int. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/all.13314","article-title":"Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial","volume":"73","author":"Thostesen","year":"2018","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2222.2007.02859.x","article-title":"Bacille-Calmette-Guerin vaccination and the development of allergic disease in children: A randomized, prospective, single-blind study","volume":"38","author":"Steenhuis","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jaci.2010.07.039","article-title":"BCG vaccination and allergy: A systematic review and meta-analysis","volume":"127","author":"Arnoldussen","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1212\/01.wnl.0000438216.93319.ab","article-title":"Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS","volume":"82","author":"Ristori","year":"2014","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Faustman, D.L., Wang, L., Okubo, Y., Burger, D., Ban, L., Man, G., Zheng, H., Schoenfeld, D., Pompei, R., and Avruch, J. (2012). Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041756"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1164\/rccm.200802-282OC","article-title":"Mortality reduction with influenza vaccine in patients with pneumonia outside \u201cflu\u201d season: Pleiotropic benefits or residual confounding?","volume":"178","author":"Eurich","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1093\/cid\/cis307","article-title":"Increased risk of noninfluenza respiratory virus infections associated with receipt of inactivated influenza vaccine","volume":"54","author":"Cowling","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1001\/archinte.167.1.53","article-title":"Influenza vaccination and risk of mortality among adults hospitalized with community-acquired pneumonia","volume":"167","author":"Spaude","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Debisarun, P.A., Gossling, K.L., Bulut, O., Kilic, G., Zoodsma, M., Liu, Z., Oldenburg, M., Ruchel, N., Zhang, B., and Xu, C.J. (2021). Induction of trained immunity by influenza vaccination\u2014Impact on COVID-19. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009928"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Consortium, E. (2020). COVID-19 Severity in Europe and the USA: Could the Seasonal Influenza Vaccination Play a Role?. Soc. Sci. Res. Netw.","DOI":"10.2139\/ssrn.3621446"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Amato, M., Werba, J.P., Frigerio, B., Coggi, D., Sansaro, D., Ravani, A., Ferrante, P., Veglia, F., Tremoli, E., and Baldassarre, D. (2020). Relationship between Influenza Vaccination Coverage Rate and COVID-19 Outbreak: An Italian Ecological Study. Vaccines, 8.","DOI":"10.3390\/vaccines8030535"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1136\/bmjebm-2020-111549","article-title":"Inactivated trivalent influenza vaccination is associated with lower mortality among patients with COVID-19 in Brazil","volume":"26","author":"Fink","year":"2020","journal-title":"BMJ Evid. Based Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.ajic.2021.02.012","article-title":"Impact of the influenza vaccine on COVID-19 infection rates and severity","volume":"49","author":"Conlon","year":"2021","journal-title":"Am. J. Infect. Control"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00285-022-01767-7","article-title":"How influenza vaccination and virus interference may impact combined influenza-coronavirus disease burden","volume":"85","author":"Alharbi","year":"2022","journal-title":"J. Math. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1093\/cid\/ciaa626","article-title":"Influenza Vaccine Does Not Increase the Risk of Coronavirus or Other Noninfluenza Respiratory Viruses: Retrospective Analysis from Canada, 2010\u20132011 to 2016\u20132017","volume":"71","author":"Skowronski","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.vaccine.2022.02.013","article-title":"Effect of the 2020\/21 season influenza vaccine on SARS-CoV-2 infection in a cohort of Italian healthcare workers","volume":"40","author":"Domnich","year":"2022","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18007","DOI":"10.1038\/s41598-018-36703-7","article-title":"Induction of Human T-cell and Cytokine Responses Following Vaccination with a Novel Influenza Vaccine","volume":"8","author":"Skibinski","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/s41598-023-28295-8","article-title":"Post-vaccination serum cytokines levels correlate with breakthrough influenza infections","volume":"13","author":"Tang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6720","DOI":"10.1038\/s41467-021-27064-3","article-title":"Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination","volume":"12","author":"Wild","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.cmi.2019.02.016","article-title":"The impact of vaccines on heterologous adaptive immunity","volume":"25","author":"Messina","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.celrep.2019.12.063","article-title":"Memory B Cell Activation, Broad Anti-influenza Antibodies, and Bystander Activation Revealed by Single-Cell Transcriptomics","volume":"30","author":"Horns","year":"2020","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41577-020-0338-x","article-title":"The non-specific and sex-differential effects of vaccines","volume":"20","author":"Aaby","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health","volume":"80","author":"Vaduganathan","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/CIRCRESAHA.118.313591","article-title":"Immunity and Inflammation in Atherosclerosis","volume":"124","author":"Wolf","year":"2019","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4944","DOI":"10.1016\/j.vaccine.2020.05.070","article-title":"Influenza vaccination as a novel means of preventing coronary heart disease: Effectiveness in older adults","volume":"38","author":"Aidoud","year":"2020","journal-title":"Vaccine"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mohammad, M.A., Tham, J., Koul, S., Rylance, R., Bergh, C., Erlinge, D., and Frobert, O. (2020). Association of acute myocardial infarction with influenza: A nationwide observational study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236866"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1136\/heartjnl-2013-304320","article-title":"Ischaemic heart disease, influenza and influenza vaccination: A prospective case control study","volume":"99","author":"Macintyre","year":"2013","journal-title":"Heart"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1093\/infdis\/jis597","article-title":"Influenza infection and risk of acute myocardial infarction in England and Wales: A CALIBER self-controlled case series study","volume":"206","author":"Hayward","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S1473-3099(09)70233-6","article-title":"Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: A systematic review","volume":"9","author":"Smeeth","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1136\/heartjnl-2015-307691","article-title":"Acute myocardial infarction and influenza: A meta-analysis of case-control studies","volume":"101","author":"Barnes","year":"2015","journal-title":"Heart"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa1702090","article-title":"Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection","volume":"378","author":"Kwong","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jchf.2018.10.011","article-title":"Effect of Influenza on Outcomes in Patients with Heart Failure","volume":"7","author":"Panhwar","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.amjcard.2020.05.045","article-title":"Influence of Influenza Infection on In-Hospital Acute Myocardial Infarction Outcomes","volume":"130","author":"Tripathi","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1177\/2047487317724009","article-title":"Severe infections and subsequent delayed cardiovascular disease","volume":"24","author":"Bergh","year":"2017","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jama.2013.279206","article-title":"Association between influenza vaccination and cardiovascular outcomes in high-risk patients: A meta-analysis","volume":"310","author":"Udell","year":"2013","journal-title":"JAMA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.jacc.2020.08.028","article-title":"Influenza Vaccination to Reduce Cardiovascular Morbidity and Mortality in Patients With COVID-19: JACC State-of-the-Art Review","volume":"76","author":"Behrouzi","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1093\/eurheartj\/ehr004","article-title":"Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome","volume":"32","author":"Phrommintikul","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/eurheartj\/ehm581","article-title":"Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study","volume":"29","author":"Ciszewski","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ehj.2003.10.018","article-title":"Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study","volume":"25","author":"Gurfinkel","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1161\/01.CIR.102.25.3039","article-title":"Association of influenza vaccination and reduced risk of recurrent myocardial infarction","volume":"102","author":"Naghavi","year":"2000","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1161\/CIRCULATIONAHA.121.057042","article-title":"Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial","volume":"144","author":"Frobert","year":"2021","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ahj.2018.05.007","article-title":"High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial","volume":"202","author":"Vardeny","year":"2018","journal-title":"Am. Heart J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jama.2020.23649","article-title":"Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients with High-Risk Cardiovascular Disease: A Randomized Clinical Trial","volume":"325","author":"Vardeny","year":"2021","journal-title":"JAMA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.1016\/j.vaccine.2007.08.039","article-title":"Effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisations for cardiovascular disease, cerebrovascular disease and pneumonia in the elderly","volume":"25","author":"Varea","year":"2007","journal-title":"Vaccine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1503\/cmaj.091891","article-title":"Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: Matched case-control study","volume":"182","author":"Siriwardena","year":"2010","journal-title":"CMAJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/eurheartj\/ehac737","article-title":"Primary prevention of acute cardiovascular events by influenza vaccination: An observational study","volume":"44","author":"Davidson","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/CIRCULATIONAHA.118.036788","article-title":"Influenza Vaccine in Heart Failure","volume":"139","author":"Modin","year":"2019","journal-title":"Circulation"},{"key":"ref_60","first-page":"326","article-title":"Influenza vaccination and risk of hospitalization in patients with heart failure: A self-controlled case series study","volume":"38","author":"Mohseni","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jchf.2015.10.012","article-title":"Influenza Vaccination in Patients With Chronic Heart Failure: The PARADIGM-HF Trial","volume":"4","author":"Vardeny","year":"2016","journal-title":"JACC Heart Fail."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e1835","DOI":"10.1016\/S2214-109X(22)00432-6","article-title":"Influenza vaccine to reduce adverse vascular events in patients with heart failure: A multinational randomised, double-blind, placebo-controlled trial","volume":"10","author":"Loeb","year":"2022","journal-title":"Lancet Glob. Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e914","DOI":"10.1016\/S2468-2667(22)00222-5","article-title":"Association between influenza vaccination and risk of stroke in Alberta, Canada: A population-based study","volume":"7","author":"Holodinsky","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1056\/NEJMoa025028","article-title":"Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly","volume":"348","author":"Nichol","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.3390\/ijerph110403639","article-title":"Association of influenza vaccination and reduced risk of stroke hospitalization among the elderly: A population-based case-control study","volume":"11","author":"Lin","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1161\/hs0202.102328","article-title":"Association between influenza vaccination and reduced risk of brain infarction","volume":"33","author":"Lavallee","year":"2002","journal-title":"Stroke"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1016\/j.vaccine.2015.08.013","article-title":"Influenza vaccination and risk of stroke: Self-controlled case-series study","volume":"33","author":"Asghar","year":"2015","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.atherosclerosis.2019.01.008","article-title":"Protective effect of influenza vaccination on outcomes in geriatric stroke patients: A nationwide matched cohort study","volume":"282","author":"Lam","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/eurheartj\/ehac826","article-title":"The ideal vaccine to prevent cardiovascular disease","volume":"44","author":"Frobert","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.acvd.2022.01.005","article-title":"Does the influenza A vaccine have a direct atheroprotective effect?","volume":"115","author":"Aidoud","year":"2022","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1016\/j.athoracsur.2020.07.052","article-title":"Influenza Vaccination Blunts the Inflammatory Response in Patients Undergoing Cardiopulmonary Bypass","volume":"111","author":"Atoui","year":"2020","journal-title":"Ann. Thorac. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e228873","DOI":"10.1001\/jamanetworkopen.2022.8873","article-title":"Association of Influenza Vaccination with Cardiovascular Risk: A Meta-analysis","volume":"5","author":"Behrouzi","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ahj.2022.10.005","article-title":"Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction\u2014Insights from the IAMI trial","volume":"255","author":"Frobert","year":"2023","journal-title":"Am. Heart J."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chorell, E., Olsson, T., Jansson, J.H., and Wennberg, P. (2020). Lysophospholipids as Predictive Markers of ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI). Metabolites, 11.","DOI":"10.3390\/metabo11010025"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1016\/j.vaccine.2014.07.007","article-title":"Influenza vaccine as prevention for cardiovascular diseases: Possible molecular mechanism","volume":"32","author":"Veljkovic","year":"2014","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1126\/science.abh1654","article-title":"Immunotherapy: Building a bridge to a cure for type 1 diabetes","volume":"373","author":"Bluestone","year":"2021","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors Collaboration, Sarwar, N., Gao, P., Seshasai, S.R., Gobin, R., Kaptoge, S., Di Angelantonio, E., Ingelsson, E., Lawlor, D.A., and Selvin, E. (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet, 375, 2215\u20132222.","DOI":"10.1016\/S0140-6736(10)60484-9"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. Health"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1093\/eurheartj\/ehab724.2626","article-title":"Prevalences and incidences of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: A nationwide observational study","volume":"42","author":"Angoulvant","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.2337\/dc13-0418","article-title":"Residual beta-Cell function 3\u20136 years after onset of type 1 diabetes reduces risk of severe hypoglycemia in children and adolescents","volume":"36","author":"Sorensen","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/bmb\/ldab027","article-title":"Immunotherapy for type 1 diabetes","volume":"140","author":"Allen","year":"2021","journal-title":"Br. Med. Bull."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fmed.2018.00283","article-title":"The Development of Immunotherapy Strategies for the Treatment of Type 1 Diabetes","volume":"5","author":"Coppieters","year":"2018","journal-title":"Front. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1753-0407.2010.00110.x","article-title":"Conversion to type 1 diabetes after H1N1 influenza infection: A case report","volume":"3","author":"Watanabe","year":"2011","journal-title":"J. Diabetes"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/adc.2009.176859","article-title":"Pandemic (H1N1) 2009: A clinical spectrum in the general paediatric population","volume":"96","author":"Larcombe","year":"2011","journal-title":"Arch. Dis. Child."},{"key":"ref_85","first-page":"161","article-title":"Is there a link between influenza and type I diabetes? Increased incidence of TID during the pandemic H1N1 influenza of 2009 in Chile","volume":"11","author":"Valdes","year":"2013","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1177\/039463201102400311","article-title":"Detection of respiratory viruses in the 2009 winter season in Rome: 2009 influenza A (H1N1) complications in children and concomitant type 1 diabetes onset","volume":"24","author":"Nenna","year":"2011","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1007\/s00125-018-4662-7","article-title":"Pandemic influenza and subsequent risk of type 1 diabetes: A nationwide cohort study","volume":"61","author":"Ruiz","year":"2018","journal-title":"Diabetologia"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00125-017-4448-3","article-title":"Pandemrix(R) vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children","volume":"61","author":"Lynch","year":"2018","journal-title":"Diabetologia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1111\/j.1464-5491.2011.03449.x","article-title":"Long-lasting immunogenicity and safety of a 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine when co-administered with a 2009\u20132010 seasonal influenza vaccine in young patients with type 1 diabetes mellitus","volume":"28","author":"Zuccotti","year":"2011","journal-title":"Diabet. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/BF00292541","article-title":"Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus","volume":"30","author":"Diepersloot","year":"1987","journal-title":"Diabetologia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5095","DOI":"10.1016\/j.vaccine.2017.07.095","article-title":"Benefits of flu vaccination for persons with diabetes mellitus: A review","volume":"35","author":"Goeijenbier","year":"2017","journal-title":"Vaccine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1073\/pnas.1904022116","article-title":"Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer","volume":"117","author":"Newman","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41574-020-00443-4","article-title":"Type 1 diabetes mellitus as a disease of the beta-cell (do not blame the immune system?)","volume":"17","author":"Roep","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.vaccine.2005.09.058","article-title":"Age-related changes in the immune response to influenza vaccination in a racially diverse, healthy elderly population","volume":"24","author":"Gardner","year":"2006","journal-title":"Vaccine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.lab.2005.03.009","article-title":"Effect of influenza vaccine on markers of inflammation and lipid profile","volume":"145","author":"Tsai","year":"2005","journal-title":"J. Lab. Clin. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1016\/j.cell.2021.05.039","article-title":"The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination","volume":"184","author":"Wimmers","year":"2021","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lopez-Olivo, M.A., Valerio, V., Karpes Matusevich, A.R., Brizio, M., Kwok, M., Geng, Y., Suarez-Almazor, M.E., and Colmegna, I. (2022). Safety and Efficacy of Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitors. Systematic Review with Meta-Analysis. Vaccines, 10.","DOI":"10.3390\/vaccines10081195"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.trecan.2021.02.006","article-title":"To Vaccinate or not: Influenza Virus and Lung Cancer Progression","volume":"7","author":"Angrini","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e18035","DOI":"10.1097\/MD.0000000000018035","article-title":"Effect of annual influenza vaccination on reducing lung cancer in patients with chronic obstructive pulmonary disease from a population-based cohort study","volume":"98","author":"Chen","year":"2019","journal-title":"Medicine"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chen, C.C., Wu, C.H., Lin, C.H., Chiu, C.C., Yang, T.Y., Lei, M.H., Yeh, H.T., Jian, W., Fang, Y.A., and Hao, W.R. (2022). Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study. Cancers, 14.","DOI":"10.3390\/cancers14122926"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/ijc.33340","article-title":"Association of postoperative influenza vaccine on overall mortality in patients undergoing curative surgery for solid tumors","volume":"148","author":"Gogenur","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"688755","DOI":"10.3389\/fonc.2021.688755","article-title":"Repurposing Infectious Diseases Vaccines against Cancer","volume":"11","author":"Vandeborne","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/cid\/ciz202","article-title":"Safety of Inactivated Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitors","volume":"70","author":"Chong","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e573","DOI":"10.1200\/JOP.19.00495","article-title":"Safety of Influenza Vaccine in Patients with Cancer Receiving Pembrolizumab","volume":"16","author":"Failing","year":"2020","journal-title":"JCO Oncol. Pract."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.2217\/imt-2018-0080","article-title":"INfluenza Vaccine Indication during therapy with Immune checkpoint inhibitors: A transversal challenge. The INVIDIa study","volume":"10","author":"Bersanelli","year":"2018","journal-title":"Immunotherapy"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2217\/imt-2019-0180","article-title":"Impact of influenza syndrome and flu vaccine on survival of cancer patients during immunotherapy in the INVIDIa study","volume":"12","author":"Bersanelli","year":"2020","journal-title":"Immunotherapy"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1158\/0008-5472.CAN-12-1993","article-title":"Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells","volume":"73","author":"Tai","year":"2013","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5104","DOI":"10.1158\/1078-0432.CCR-13-0246","article-title":"Perioperative influenza vaccination reduces postoperative metastatic disease by reversing surgery-induced dysfunction in natural killer cells","volume":"19","author":"Tai","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e1431082","DOI":"10.1080\/2162402X.2018.1431082","article-title":"Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity","volume":"7","author":"Tai","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1089\/jir.2018.0019","article-title":"Cytokines in the Treatment of Cancer","volume":"39","author":"Conlon","year":"2019","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/imcb.12301","article-title":"The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer\u2019s disease","volume":"98","author":"Webers","year":"2020","journal-title":"Immunol. Cell Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"101534","DOI":"10.1016\/j.arr.2021.101534","article-title":"Influenza vaccination reduces dementia risk: A systematic review and meta-analysis","volume":"73","author":"Veronese","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e2868","DOI":"10.1097\/MD.0000000000002868","article-title":"Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study","volume":"95","author":"Liu","year":"2016","journal-title":"Medicine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/jim-2019-001155","article-title":"Influenza vaccination reduces dementia in patients with chronic obstructive pulmonary disease: A nationwide cohort study","volume":"68","author":"Luo","year":"2020","journal-title":"J. Investig. Med."},{"key":"ref_116","first-page":"1495","article-title":"Past exposure to vaccines and subsequent risk of Alzheimer\u2019s disease","volume":"165","author":"Verreault","year":"2001","journal-title":"CMAJ"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.3233\/JAD-220361","article-title":"Risk of Alzheimer\u2019s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching","volume":"88","author":"Bukhbinder","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12974-020-01741-4","article-title":"Influenza vaccination in early Alzheimer\u2019s disease rescues amyloidosis and ameliorates cognitive deficits in APP\/PS1 mice by inhibiting regulatory T cells","volume":"17","author":"Yang","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/gerona\/glab115","article-title":"Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination","volume":"76","author":"Scherrer","year":"2021","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.21873\/invivo.12622","article-title":"Herpes Zoster Vaccination Reduces Risk of Dementia","volume":"35","author":"Lehrer","year":"2021","journal-title":"In Vivo"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Klinger, D., Hill, B.L., Barda, N., Halperin, E., Gofrit, O.N., Greenblatt, C.L., Rappoport, N., Linial, M., and Bercovier, H. (2021). Bladder Cancer Immunotherapy by BCG Is Associated with a Significantly Reduced Risk of Alzheimer\u2019s Disease and Parkinson\u2019s Disease. Vaccines, 9.","DOI":"10.1101\/2021.01.30.21250811"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e409","DOI":"10.1016\/j.clgc.2021.05.001","article-title":"Intravesical Bacillus Calmette-Guerin Treatment Is Inversely Associated with the Risk of Developing Alzheimer Disease or Other Dementia among Patients with Non-Muscle-Invasive Bladder Cancer","volume":"19","author":"Kim","year":"2021","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_123","unstructured":"(CDC) CfDCaP (2023, June 26). Seasonal Influenza Vaccine Safety: A Summary for Clinicians, Available online: https:\/\/www.cdc.gov\/flu\/professionals\/vaccination\/vaccine_safety.htm."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","article-title":"The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives","volume":"14","author":"Tsalamandris","year":"2019","journal-title":"Eur. Cardiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s10194-021-01271-1","article-title":"Migraine and neuroinflammation: The inflammasome perspective","volume":"22","author":"Kursun","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"aaf9194","DOI":"10.1126\/scitranslmed.aaf9194","article-title":"Influenza vaccines differentially regulate the interferon response in human dendritic cell subsets","volume":"9","author":"Athale","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S1473-3099(16)00129-8","article-title":"Variable influenza vaccine effectiveness by subtype: A systematic review and meta-analysis of test-negative design studies","volume":"16","author":"Belongia","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wiggins, K.B., Smith, M.A., and Schultz-Cherry, S. (2021). The Nature of Immune Responses to Influenza Vaccination in High-Risk Populations. Viruses, 13.","DOI":"10.3390\/v13061109"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/9\/1419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:56Z","timestamp":1760128736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/9\/1419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":128,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["vaccines11091419"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11091419","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,25]]}}}