{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:54:14Z","timestamp":1787162054829,"version":"build-2736575974"},"reference-count":232,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"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>Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the case that the efficiency of this vaccine is lower in older than younger adults, this is not always true, and the reasons for the differential responses are manifold. Undoubtedly, changes in the innate and adaptive immune response with ageing are associated with failure to respond to the influenza vaccine, but the cause is unclear. Moreover, recent advances in vaccine formulations and adjuvants, as well as in our understanding of immune changes with ageing, have contributed to the development of vaccines, such as those against herpes zoster and SARS-CoV-2, that can protect against serious disease in older adults just as well as in younger people. In the present article, we discuss the reasons why it is a myth that vaccines inevitably protect less well in older individuals, and that vaccines represent one of the most powerful means to protect the health and ensure the quality of life of older adults.<\/jats:p>","DOI":"10.3390\/vaccines10040607","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T23:07:16Z","timestamp":1649891236000},"page":"607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change"],"prefix":"10.3390","volume":"10","author":[{"given":"Tamas","family":"Fulop","sequence":"first","affiliation":[{"name":"Research Center on Aging, Geriatric Division, Department of Medicine, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anis","family":"Larbi","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-0163","authenticated-orcid":false,"given":"Graham","family":"Pawelec","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of T\u00fcbingen, 72072 T\u00fcbingen, Germany"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Groupe de Recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, 3001 12e Ave N, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Provost","sequence":"additional","affiliation":[{"name":"Ikerbasque, The Basque Foundation for Science, 48009 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0817-3160","authenticated-orcid":false,"given":"Abedelouahed","family":"Khalil","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Geriatric Division, Department of Medicine, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Geriatric Division, Department of Medicine, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafim","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Ikerbasque, The Basque Foundation for Science, 48009 Bilbao, Spain"},{"name":"BCAM\u2014The Basque Center for Applied Mathematics, 48009 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9325-4207","authenticated-orcid":false,"given":"Mathieu","family":"Desroches","sequence":"additional","affiliation":[{"name":"MathNeuro Team, Inria Sophia Antipolis M\u00e9diterran\u00e9e, CEDEX, 06902 Sophia Antipolis, France"},{"name":"The Jean Alexandre Dieudonn\u00e9 Laboratory, Universit\u00e9 C\u00f4te d\u2019Azur, CEDEX 2, 06108 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuiku","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"Institute of Health and Life Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Franceschi","sequence":"additional","affiliation":[{"name":"IRCCS Institute of Neurological Sciences of Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"},{"name":"Department of Applied Mathematics and Laboratory of Systems Biology of Healthy Aging, Lobachevsky State University, 603000 Nizhny Novgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek M.","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1073\/pnas.1400472111","article-title":"History of vaccination","volume":"111","author":"Plotkin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3389\/fimmu.2020.00717","article-title":"Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives","volume":"11","author":"Wagner","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"n188","DOI":"10.1136\/bmj.n188","article-title":"Vaccines for older adults","volume":"372","author":"Cunningham","year":"2021","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12979-021-00249-6","article-title":"Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond","volume":"18","author":"Weinberger","year":"2021","journal-title":"Immun. Ageing"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/d41586-020-02483-2","article-title":"The coronavirus is most deadly if you are older and male\u2014New data reveal the risks","volume":"585","author":"Mallapaty","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.jaci.2020.03.017","article-title":"Influence of immune aging on vaccine responses","volume":"145","author":"Gustafson","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity","volume":"183","author":"Ramirez","year":"2020","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eabc8511","DOI":"10.1126\/science.abc8511","article-title":"Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications","volume":"369","author":"Mathew","year":"2020","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.abb0762","article-title":"Aging immunity may exacerbate COVID-19","volume":"369","author":"Akbar","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1172\/JCI144115","article-title":"Age-related susceptibility to coronavirus infections: Role of impaired and dysregulated host immunity","volume":"130","author":"Channappanavar","year":"2020","journal-title":"Clin. Invest."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00011-020-01372-8","article-title":"The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: The contribution of \u201cinflame-aging\u201d","volume":"69","author":"Meftahi","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/j.1365-2796.2009.02201.x","article-title":"Influenza vaccines provide diminished protection but are cost-saving in older adults","volume":"267","author":"Deans","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.coi.2009.05.023","article-title":"Immunosenescence: What does it mean to health outcomes in older adults?","volume":"21","author":"McElhaney","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1056\/NEJMoa022678","article-title":"Effectiveness of pneumococcal polysaccharide vaccine in older adults","volume":"348","author":"Jackson","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exger.2017.10.024","article-title":"Age and immunity: What is \u201cimmunosenescence\u201d?","volume":"105","author":"Pawelec","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-13-3681-2_2","article-title":"The Immune System and Its Dysregulation with Aging","volume":"91","author":"Pawelec","year":"2019","journal-title":"Subcell Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging: An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.3389\/fimmu.2017.01960","article-title":"Immunosenescence and Inflamm-Aging as Two Sides of the Same Coin: Friends or Foes?","volume":"8","author":"Fulop","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.smim.2018.10.010","article-title":"Vaccination in the elderly: The challenge of immune changes with aging","volume":"40","author":"Ciabattini","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"982","DOI":"10.3389\/fimmu.2017.00982","article-title":"Immunobiography and the Heterogeneity of Immune Responses in the Elderly: A Focus on Inflammaging and Trained Immunity","volume":"8","author":"Franceschi","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/infdis\/jix282","article-title":"The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People","volume":"216","author":"Andrew","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.vaccine.2012.01.015","article-title":"The unmet need in the elderly: How immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines","volume":"30","author":"McElhaney","year":"2012","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.rmr.2018.02.015","article-title":"History and principles of vaccination","volume":"36","author":"Launay","year":"2019","journal-title":"Rev. Mal. Respir."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-4939-3387-7_3","article-title":"Principles of Vaccination","volume":"1403","author":"Zepp","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cakala-Jakimowicz, M., Kolodziej-Wojnar, P., and Puzianowska-Kuznicka, M. (2021). Aging-Related Cellular, Structural and Functional Changes in the Lymph Nodes: A Significant Component of Immunosenescence? An Overview. Cells, 10.","DOI":"10.3390\/cells10113148"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C2","DOI":"10.1016\/j.vaccine.2010.07.022","article-title":"Key concepts in immunology","volume":"28","author":"Moser","year":"2010","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0092-8674(01)00455-X","article-title":"Regulation of T cell immunity by dendritic cells","volume":"106","author":"Lanzavecchia","year":"2001","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nature02238","article-title":"T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases","volume":"427","author":"Mempel","year":"2004","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.it.2005.11.005","article-title":"Triggering TLR signaling in vaccination","volume":"27","author":"Medzhitov","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.0105-2896.2004.00144.x","article-title":"Modulating vaccine responses with dendritic cells and Toll-like receptors","volume":"199","author":"Pulendran","year":"2004","journal-title":"Immunol Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"Plotkin","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.coi.2005.04.010","article-title":"Understanding the generation and function of memory T cell subsets","volume":"17","author":"Lanzavecchia","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/icb.2008.13","article-title":"Influencing the fates of CD4 T cells on the path to memory: Lessons from influenza","volume":"86","author":"Strutt","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/imr.12032","article-title":"Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets","volume":"252","author":"Yamane","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.coi.2012.01.014","article-title":"Helper T cell diversity and plasticity","volume":"24","author":"Nakayamada","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/ni.2038","article-title":"Origins of CD4(+) effector and central memory T cells","volume":"12","author":"Pepper","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3389\/fimmu.2013.00421","article-title":"CD4(+) T Cell Priming as Biomarker to Study Immune Response to Preventive Vaccines","volume":"4","author":"Ciabattini","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1615\/CritRevImmunol.2014010373","article-title":"CD4 T-cell memory generation and maintenance","volume":"34","author":"Gasper","year":"2014","journal-title":"Crit. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.smim.2007.12.001","article-title":"Follicular dendritic cell networks of primary follicles and germinal centers: Phenotype and function","volume":"20","author":"Allen","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s11882-014-0434-8","article-title":"B cell biology: An overview","volume":"14","author":"Eibel","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.imlet.2017.02.012","article-title":"Understanding memory CD8+ T cells","volume":"185","author":"Samji","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.ebiom.2015.07.029","article-title":"Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians","volume":"2","author":"Arai","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111672","DOI":"10.1016\/j.mad.2022.111672","article-title":"Immunosenescence and COVID-19","volume":"204","author":"Witkowski","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fmed.2018.00061","article-title":"The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different","volume":"5","author":"Franceschi","year":"2018","journal-title":"Front. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13028","DOI":"10.1111\/acel.13028","article-title":"Reversal of epigenetic aging and immunosenescent trends in humans","volume":"18","author":"Fahy","year":"2019","journal-title":"Aging Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"573","DOI":"10.18632\/aging.101414","article-title":"An epigenetic biomarker of aging for lifespan and healthspan","volume":"10","author":"Levine","year":"2018","journal-title":"Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E4104","DOI":"10.1073\/pnas.1506264112","article-title":"Quantification of biological aging in young adults","volume":"112","author":"Belsky","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A.A., Hirokawa, K., Witkowski, J.M., and Franceschi, C. (2021). Immunology of Aging: The Birth of Inflammaging. Clin. Rev. Allergy Immunol.","DOI":"10.1007\/s12016-021-08899-6"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s11912-021-01097-9","article-title":"Determination of Biological Age: Geriatric Assessment vs. Biological Biomarkers","volume":"23","author":"Diebel","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.3389\/fimmu.2020.01683","article-title":"Systems Biology Approaches to Understanding the Human Immune System","volume":"11","author":"Dhillon","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1586\/erv.12.61","article-title":"Understanding the immuneresponse to seasonal influenza vaccination in older adults: A systems biology approach","volume":"11","author":"Lambert","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110632","DOI":"10.1016\/j.exger.2019.110632","article-title":"Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses","volume":"124","author":"Crooke","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eaay4014","DOI":"10.1126\/science.aay4014","article-title":"The science and medicine of humanimmunology","volume":"369","author":"Pulendran","year":"2020","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s10654-021-00767-z","article-title":"Immune age and biological age as determinants of vaccine responsiveness among elderly populations: The Human Immunomics Initiative research program","volume":"36","author":"Goudsmit","year":"2021","journal-title":"Eur. J. Epidemiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coviro.2020.09.007","article-title":"Immunity to acute virus infections with advanced age","volume":"46","author":"Bradshaw","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/0024-3205(89)90482-7","article-title":"Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: Cross-sectional and longitudinal studies","volume":"44","author":"Niwa","year":"1989","journal-title":"Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/jlb.67.1.40","article-title":"Effect of age on human neutrophil function","volume":"67","author":"Wenisch","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3389\/fimmu.2017.00896","article-title":"Role of Dendritic Cells in Inflammation and Loss of Tolerance in the Elderly","volume":"8","author":"Agrawal","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1474-9728.2004.00102.x","article-title":"Innate immunity in aging: Impact on macrophage function","volume":"3","author":"Plowden","year":"2004","journal-title":"Aging Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.imlet.2014.06.015","article-title":"Proinflammatory status influences NK cells subsets in the elderly","volume":"162","author":"Campos","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/imr.12725","article-title":"Emerging insights into human health and NK cell biology from the study of NK cell deficiencies","volume":"287","author":"Mace","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1159\/000497375","article-title":"Human Inflammaging","volume":"65","author":"Larbi","year":"2019","journal-title":"Gerontology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.smim.2012.04.008","article-title":"Innate immunosenescence: Effect of aging on cells and receptors of the innateimmunesystem in humans","volume":"24","author":"Solana","year":"2012","journal-title":"Semin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/intimm\/dxl119","article-title":"Effects of TREM-1 activation in human neutrophils: Activation of signaling pathways, recruitment into lipid rafts and association with TLR4","volume":"19","author":"Fortin","year":"2007","journal-title":"Int. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/acel.12320","article-title":"Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors","volume":"14","author":"Metcalf","year":"2015","journal-title":"Aging Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ircmb.2019.07.004","article-title":"Dendritic cell subsets and locations","volume":"348","author":"Balan","year":"2019","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.exger.2013.12.009","article-title":"Role of dendriticn cells in innate and adaptive immune response in humanaging","volume":"54","author":"Gupta","year":"2014","journal-title":"Exp. Gerontol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/08830185.2020.1844195","article-title":"Dendritic cells in COVID-19 immunopathogenesis: Insights for a possible role in determining disease outcome","volume":"40","author":"Borges","year":"2021","journal-title":"Int. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.exger.2006.11.007","article-title":"Dendritic cells in human aging","volume":"42","author":"Agrawal","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/j.1469-7580.2010.01213.x","article-title":"Age-dependent histoarchitectural changes in human lymph nodes: An underestimated process with clinical relevance?","volume":"216","author":"Hadamitzky","year":"2010","journal-title":"J. Anat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11357-010-9191-3","article-title":"Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity","volume":"33","author":"Sridharan","year":"2011","journal-title":"Age"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/acel.12384","article-title":"Reduced na\u00efve CD8(+) T-cell priming efficacy in elderly adults","volume":"15","author":"Lissina","year":"2016","journal-title":"Aging Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1365-2567.2004.02006.x","article-title":"Age-related loss of na\u00efve T cells and dysregulation of T-cell\/B-cell interactions in human lymph nodes","volume":"114","author":"Lazuardi","year":"2005","journal-title":"Immunology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.clim.2007.12.002","article-title":"T cell subset-specific susceptibility to aging","volume":"127","author":"Lee","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Whiting, C.C., Siebert, J., Newman, A.M., Du, H.-W., Alizadeh, A.A., Goronzy, J., Weyand, C.M., Krishnan, E., Fathman, C.G., and Maecker, H.T. (2015). Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133627"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1399-0039.2007.00891.x","article-title":"Immunosenescence: Deficits in adaptive immunity in the elderly","volume":"70","author":"Hakim","year":"2007","journal-title":"Tissue Antigens"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.coviro.2021.09.017","article-title":"Understanding T cell aging to improve anti-viral immunity","volume":"51","author":"Zhang","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"103998","DOI":"10.1016\/j.cellimm.2019.103998","article-title":"Aging and influenza vaccine-induced immunity","volume":"348","author":"Dugan","year":"2020","journal-title":"Cell Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2249.2008.03785.x","article-title":"Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals","volume":"155","author":"Chidrawar","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/eji.201546178","article-title":"Aging of the immune system: Focus on inflammation and vaccination","volume":"46","author":"Pinti","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.4049\/jimmunol.1102514","article-title":"Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation","volume":"188","author":"Longo","year":"2012","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.cels.2016.09.009","article-title":"Defective Signaling in the JAK-STAT Pathway Tracks with Chronic Inflammation and Cardiovascular Risk in Aging Humans","volume":"3","author":"Furman","year":"2016","journal-title":"Cell Syst."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"865","DOI":"10.4049\/jimmunol.1402389","article-title":"Age-Associated Failure to Adjust Type I IFN Receptor Signaling Thresholds after T Cell Activation","volume":"195","author":"Li","year":"2015","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41590-020-0643-3","article-title":"Sestrins induce natural killer function in senescent-like CD8+ T cells","volume":"21","author":"Pereira","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.immuni.2020.11.005","article-title":"Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging","volume":"54","author":"Mogilenko","year":"2021","journal-title":"Immunity"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.immuni.2018.02.010","article-title":"Understanding Subset Diversity in T Cell Memory","volume":"48","author":"Jameson","year":"2018","journal-title":"Immunity"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1742-4933-5-6","article-title":"Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people","volume":"5","author":"Koch","year":"2008","journal-title":"Immun. Ageing"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7123","DOI":"10.1111\/febs.15770","article-title":"Hallmarks of the aging T-cell system","volume":"288","author":"Zhang","year":"2021","journal-title":"FEBS J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","article-title":"Mechanisms underlying T cell ageing","volume":"19","author":"Goronzy","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e12957","DOI":"10.1111\/acel.12957","article-title":"Transcription factor networks in aged na\u00efve CD4 T cells bias lineage differentiation","volume":"18","author":"Hu","year":"2019","journal-title":"Aging Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.20161066","article-title":"Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1","volume":"215","author":"Jeng","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.it.2009.03.013","article-title":"CD28(-) T cells: Their role in the age-associated decline of immune function","volume":"30","author":"Weng","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/cyto.a.22351","article-title":"From \u201ctruly na\u00efve\u201d to \u201cexhausted senescent\u201d T cells: When markers predict functionality","volume":"85","author":"Larbi","year":"2014","journal-title":"Cytom. A"},{"key":"ref_94","first-page":"271","article-title":"Human T cell aging and the impact of persistent viral infections","volume":"4","author":"Larbi","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.arr.2010.08.003","article-title":"Persistent viral infections and immune aging","volume":"10","author":"Brunner","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nri.2015.3","article-title":"Tissue-resident memory T cells: Local specialists in immune defence","volume":"16","author":"Mueller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41591-019-0381-y","article-title":"A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring","volume":"25","author":"Alpert","year":"2019","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.coi.2010.06.011","article-title":"Immune memory and aging: An infinite or finite resource?","volume":"22","author":"Rudd","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"111357","DOI":"10.1016\/j.mad.2020.111357","article-title":"The conundrum of human immune system \u201csenescence\u201d","volume":"192","author":"Pawelec","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.mad.2016.12.008","article-title":"Inflammaging and human longevity in the omics era","volume":"165","author":"Monti","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1080\/21645515.2017.1343226","article-title":"Influenza vaccination in the elderly","volume":"14","author":"Smetana","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"101422","DOI":"10.1016\/j.arr.2021.101422","article-title":"Immunosenescence and inflammaging in the aging process: Age-related diseases or longevity?","volume":"71","author":"Santoro","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev-cellbio-011620-034148","article-title":"B Cell Immunosenescence","volume":"36","author":"Frasca","year":"2020","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/imr.12864","article-title":"Age-related factors that affect B cell responses to vaccination in mice and humans","volume":"296","author":"Frasca","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.it.2009.04.005","article-title":"B cells and aging: Molecules and mechanisms","volume":"30","author":"Cancro","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.exger.2017.07.002","article-title":"Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses","volume":"107","author":"Frasca","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12979-020-00210-z","article-title":"Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination","volume":"17","author":"Frasca","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/eji.201444878","article-title":"Plasma cell numbers decrease in bone marrow of old patients","volume":"45","author":"Pritz","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1474-9726.2008.00443.x","article-title":"B-cell diversity decreases in old age and is correlated with poor health status","volume":"8","author":"Gibson","year":"2009","journal-title":"Aging Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nri2508","article-title":"B-cell responses to vaccination at the extremes of age","volume":"9","author":"Siegrist","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.3389\/fimmu.2019.02247","article-title":"Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention","volume":"10","author":"Aiello","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.cell.2016.07.050","article-title":"Epigenetic Mechanisms of Longevity and Aging","volume":"166","author":"Sen","year":"2016","journal-title":"Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigeneticclock theory of ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"585168","DOI":"10.3389\/fimmu.2020.585168","article-title":"Distinct Age-Related Epigenetic Signatures in CD4 and CD8 T Cells","volume":"11","author":"Hu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1084\/jem.20170416","article-title":"The chromatin accessibility signature of human immune aging stems from CD8+ T cells","volume":"214","author":"Ucar","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eaag0192","DOI":"10.1126\/sciimmunol.aag0192","article-title":"Epigenomics of human CD8 T cell differentiation and aging","volume":"2","author":"Moskowitz","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri1440","article-title":"Will telomere erosion lead to a loss of T-cell memory?","volume":"4","author":"Akbar","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1134\/S0006297921120026","article-title":"Is Evidence Supporting the Subtelomere-Telomere Theory of Aging?","volume":"86","author":"Libertini","year":"2021","journal-title":"Biochemistry (Mosc)"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"957","DOI":"10.18632\/aging.100705","article-title":"Age-associated changes in basal NF-\u03baB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase","volume":"6","author":"Bektas","year":"2014","journal-title":"Aging"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cmet.2020.04.015","article-title":"Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation","volume":"32","author":"Bharath","year":"2020","journal-title":"Cell Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-immunol-042617-053019","article-title":"Unraveling the Complex Interplay between T Cell Metabolism and Function","volume":"36","author":"Geltink","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nm.2963","article-title":"Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity","volume":"18","author":"Li","year":"2012","journal-title":"Nat. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1478-811X-12-2","article-title":"Downregulation of inhibitory SRC homology 2 domain-containing phosphatase-1 (SHP-1) leads to recovery of T cell responses in elderly","volume":"12","author":"Fortin","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coi.2014.05.007","article-title":"Cellular signaling in the aging immune system","volume":"29","author":"Fulop","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.cellsig.2005.08.016","article-title":"Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging","volume":"18","author":"Larbi","year":"2006","journal-title":"Cell Signal."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Smigielska-Czepiel, K., Berg, A.V.D., Jellema, P., Slezak-Prochazka, I., Maat, H., Bos, H.V.D., Van Der Lei, R.J., Kluiver, J., Brouwer, E., and Boots, A.M.H. (2013). Dual role of miR-21 in CD4+ T-cells: Activation-induced miR-21 supports survival of memory T-cells and regulates CCR7 expression in naive T-cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076217"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1016\/j.celrep.2018.10.074","article-title":"Activation of miR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells","volume":"25","author":"Kim","year":"2018","journal-title":"Cell Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mad.2006.11.016","article-title":"Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans","volume":"128","author":"Franceschi","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"ref_130","first-page":"84","article-title":"The Role of Immunosenescence in the Development of Age-Related Diseases","volume":"68","author":"Dupuis","year":"2016","journal-title":"Rev. Investig. Clin."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.smim.2018.09.003","article-title":"The integration of inflammaging in age-related diseases","volume":"40","author":"Fulop","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"10369","DOI":"10.1038\/ncomms10369","article-title":"Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination","volume":"7","author":"Fourati","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jaci.2017.10.032","article-title":"Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation","volume":"142","author":"Chambers","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"583019","DOI":"10.3389\/fimmu.2020.583019","article-title":"Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly","volume":"11","author":"Pereira","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"13139","DOI":"10.1073\/pnas.1409155111","article-title":"Diversity and clonal selection in the human T-cell repertoire","volume":"111","author":"Qi","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1182\/blood-2009-04-217604","article-title":"Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells","volume":"114","author":"Robins","year":"2009","journal-title":"Blood"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e49900","DOI":"10.7554\/eLife.49900","article-title":"The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes","volume":"9","author":"Oakes","year":"2020","journal-title":"Elife"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/RTI.0000000000000349","article-title":"Age-stratified Patterns of Thymic Involution on Multidetector CT","volume":"33","author":"Drabkin","year":"2018","journal-title":"J. Thorac. Imaging"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Mold, J.E., R\u00e9u, P., Olin, A., Bernard, S., Micha\u00eblsson, J., Rane, S., Yates, A., Khosravi, A., Salehpour, M., and Possnert, G. (2019). Cell generation dynamics underlying naive T-cell homeostasis in adult humans. PLoS Biol., 17.","DOI":"10.1101\/635995"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"103852","DOI":"10.1016\/j.ebiom.2022.103852","article-title":"Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: Results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old","volume":"76","author":"Nicoli","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.4049\/jimmunol.1302064","article-title":"Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling","volume":"192","author":"Britanova","year":"2014","journal-title":"J. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Horn, V., Semmler, M., and Schweppe, C. (2021). Older People in Germany During the COVID-19 Pandemic: The Least, the More, and the Most Affected. J. Popul. Ageing.","DOI":"10.1007\/s12062-021-09352-4"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Maltese, G., Corsonello, A., Di Rosa, M., Soraci, L., Vitale, C., Corica, F., and Lattanzio, F. (2020). Frailty and COVID-19: A Systematic Scoping Review. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072106"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.jamda.2020.06.008","article-title":"Frailty and Mortality in Hospitalized Older Adults With COVID-19: Retrospective Observational Study","volume":"21","author":"Mellaerts","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10522-015-9615-7","article-title":"From inflamm-aging to immune-paralysis: A slippery slope during aging for immune-adaptation","volume":"17","author":"Fulop","year":"2016","journal-title":"Biogerontology"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Bindu, S., Dandapat, S., Manikandan, R., Dinesh, M., Subbaiyan, A., Mani, P., Dhawan, M., Tiwari, R., Bilal, M., and Bin Emran, T. (2022). Prophylactic and therapeutic insights into trained immunity: A renewed concept of innate immune memory. Hum. Vaccin. Immunother.","DOI":"10.1080\/21645515.2022.2040238"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e29892","DOI":"10.2196\/29892","article-title":"Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study","volume":"11","author":"Ietto","year":"2022","journal-title":"JMIR Res. Protoc."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"13763","DOI":"10.1073\/pnas.231499798","article-title":"Degeneracy and complexity in biological systems","volume":"98","author":"Edelman","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41589-018-0130-4","article-title":"T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability","volume":"14","author":"Riley","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1615\/CritRevImmunol.v32.i4.50","article-title":"Cross-reactivity of T cells and its role in the immune system","volume":"32","author":"Petrova","year":"2012","journal-title":"Crit. Rev. Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biosystems.2013.03.014","article-title":"Robustness and aging\u2014A systems-level perspective","volume":"112","author":"Kriete","year":"2013","journal-title":"Biosystems"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"21432","DOI":"10.1073\/pnas.1209283110","article-title":"Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age","volume":"109","author":"Johnson","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00281-020-00824-x","article-title":"The untwining of immunosenescence and aging","volume":"42","author":"Xu","year":"2020","journal-title":"Semin, Immunopathol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Verschoor, C.P., Andrew, M.K., Loeb, M., Pawelec, G., Haynes, L., Kuchel, G.A., and McElhaney, J.E. (2021). Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults. Vaccines, 9.","DOI":"10.3390\/vaccines9010025"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"681449","DOI":"10.3389\/fimmu.2021.681449","article-title":"Aging and Options to Halt Declining Immunity to Virus Infections","volume":"12","author":"Osterhaus","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"200258","DOI":"10.1183\/16000617.0258-2020","article-title":"Influenza vaccination: Protecting the most vulnerable","volume":"30","author":"Tanner","year":"2021","journal-title":"Eur. Respir Rev."},{"key":"ref_159","first-page":"CD001269","article-title":"Vaccines for preventing influenza in healthy adults","volume":"2","author":"Demicheli","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_160","unstructured":"(2022, February 11). Available online: https:\/\/www.influenza.org.nz\/."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1189\/jlb.5MA0517-207R","article-title":"Perturbed CD8(+) T cell immunity across universal influenza epitopes in the elderly","volume":"103","author":"Nguyen","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e12960","DOI":"10.1111\/acel.12960","article-title":"Transcriptomic analysis of human IL-7 receptor alpha (low) and (high) effector memory CD8(+) T cells reveals an age-associated signature linked to influenza vaccine response in older adults","volume":"18","author":"Park","year":"2019","journal-title":"Aging Cell"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.vaccine.2005.08.105","article-title":"Antibody response to influenza vaccination in the elderly: A quantitative review","volume":"24","author":"Goodwin","year":"2006","journal-title":"Vaccine"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12979-020-00181-1","article-title":"The immune response to influenza in older humans: Beyond immune senescence","volume":"17","author":"McElhaney","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.chom.2019.01.002","article-title":"Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals","volume":"25","author":"Henry","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1056\/NEJMoa1315727","article-title":"Efficacy of high-dose versus standard-dose influenza vaccine in older adults","volume":"371","author":"DiazGranados","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"A24","DOI":"10.1016\/j.vaccine.2020.09.004","article-title":"Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: An updated systematic review and meta-analysis","volume":"39","author":"Lee","year":"2021","journal-title":"Vaccine"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3947\/ic.2013.45.2.159","article-title":"Fluad-MF59-Adjuvanted Influenza Vaccine in Older Adults","volume":"45","author":"Tsai","year":"2013","journal-title":"Infect. Chemother."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.vaccine.2016.12.011","article-title":"Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis","volume":"35","author":"Domnich","year":"2017","journal-title":"Vaccine"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S1473-3099(20)30694-0","article-title":"Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: A randomised, controlled, multicentre, phase 3 efficacy study","volume":"21","author":"Beran","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa1608862","article-title":"PSC12 Study Team. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older","volume":"376","author":"Dunkle","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1086\/652144","article-title":"Immunogenicity and safety of intradermal influenza vaccination in healthy older adults","volume":"50","author":"Chi","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exger.2017.09.015","article-title":"Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage","volume":"107","author":"Merani","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_174","first-page":"1525","article-title":"Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis","volume":"219","author":"Ng","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1093\/cid\/ciz1034","article-title":"Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial","volume":"71","author":"Cowling","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.coph.2018.03.014","article-title":"Adjuvant strategies to improve vaccination of the elderly population","volume":"41","author":"Weinberger","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Falkenhorst, G., Remschmidt, C., Harder, T., Hummers-Pradier, E., Wichmann, O., and Bogdan, C. (2017). Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169368"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.vaccine.2016.02.023","article-title":"Efficacy of 23-valent pneumococcal polysaccharide vaccine in preventing community-acquired pneumonia among immunocompetent adults: A systematic review and meta-analysis of randomized trials","volume":"34","author":"Diao","year":"2016","journal-title":"Vaccine"},{"key":"ref_179","first-page":"CD000422","article-title":"Vaccines for preventing pneumococcal infection in adults","volume":"2013","author":"Moberley","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fimmu.2012.00193","article-title":"Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination","volume":"3","author":"Wu","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Berild, J.D., Winje, B.A., Vestrheim, D.F., Slotved, H.-C., Valentiner-Branth, P., Roth, A., and Stors\u00e4ter, J. (2020). A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population. Pathogens, 9.","DOI":"10.3390\/pathogens9040259"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.1016\/j.vaccine.2019.05.065","article-title":"A post-hoc analysis of serotype-specific vaccine efficacy of 13-valent pneumococcal conjugate vaccine against clinical community acquired pneumonia from a randomized clinical trial in the Netherlands","volume":"37","author":"Gessner","year":"2019","journal-title":"Vaccine"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1016\/j.vaccine.2021.02.069","article-title":"Invasive pneumococcal disease in Canada 2010\u20132017: The role of current and next-generation higher-valent pneumococcal conjugate vaccines","volume":"39","author":"Dion","year":"2021","journal-title":"Vaccine"},{"key":"ref_184","first-page":"1498","article-title":"Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design","volume":"67","author":"McLaughlin","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1056\/NEJMoa1408544","article-title":"Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults","volume":"372","author":"Bonten","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nri2494","article-title":"Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines","volume":"9","author":"Pollard","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Lewnard, J.A., Bruxvoort, K.J., Fischer, H., Hong, V.X., Grant, L.R., J\u00f3dar, L., Can\u00e9, A., Gessner, B.D., and Tartof, S.Y. (2021). Effectiveness of 13-valent pneumococcal conjugate vaccine against medically-attended lower respiratory tract infection and pneumonia among older adults. Clin. Infect. Dis., ciab1051.","DOI":"10.1101\/2021.06.30.21259721"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"7494","DOI":"10.1016\/j.vaccine.2021.10.032","article-title":"A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults \u226565 years of age with different prior pneumococcal vaccination","volume":"39","author":"Cannon","year":"2021","journal-title":"Vaccine"},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Essink, B., Sabharwal, C., Cannon, K., Frenck, R., Lal, H., Xu, X., Sundaraiyer, V., Peng, Y., Moyer, L., and Pride, M.W. (2021). Pivotal Phase 3 Randomized Clinical Trial of the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate Vaccine in Adults 18 Years and Older. Clin. Infect. Dis., ciab990.","DOI":"10.1093\/cid\/ciab990"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e768","DOI":"10.1093\/cid\/ciaa1480","article-title":"Serotype Patterns of Pneumococcal Disease in Adults Are Correlated with Carriage Patterns in Older Children","volume":"72","author":"Wyllie","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"4401","DOI":"10.1016\/j.vaccine.2019.06.008","article-title":"Effectiveness of the herpes zoster vaccine Zostavax\u00ae in Stockholm County, Sweden","volume":"37","author":"Blom","year":"2019","journal-title":"Vaccine"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1080\/21645515.2018.1560918","article-title":"Immune responses to zoster vaccines","volume":"15","author":"Levin","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1056\/NEJMoa1501184","article-title":"Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults","volume":"372","author":"Lal","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1080\/21645515.2018.1442162","article-title":"Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults","volume":"14","author":"Schwarz","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/infdis\/jiy514","article-title":"Persistence of Varicella-Zoster Virus Cell-Mediated Immunity after the Administration of a Second Dose of Live Herpes Zoster Vaccine","volume":"219","author":"Weinberg","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.coi.2019.02.009","article-title":"Understanding the immunology of Shingrix, a recombinant glycoprotein E adjuvanted herpes zoster vaccine","volume":"59","author":"Heineman","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.coi.2019.02.005","article-title":"Understanding the immunology of the Zostavax shingles vaccine","volume":"59","author":"Sullivan","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa2028436","article-title":"Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults","volume":"383","author":"Anderson","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1016\/S0140-6736(20)32466-1","article-title":"Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): A single-blind, randomised, controlled, phase 2\/3 trial","volume":"396","author":"Ramasamy","year":"2021","journal-title":"Lancet"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Salvagno, G.L., Henry, B.M., di Piazza, G., Pighi, L., De Nitto, S., Bragantini, D., Gianfilippi, G., and Lippi, G. (2021). Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination. Diagnostics, 11.","DOI":"10.2139\/ssrn.3823718"},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Sasso, B.L., Giglio, R., Vidali, M., Scazzone, C., Bivona, G., Gambino, C., Ciaccio, A., Agnello, L., and Ciaccio, M. (2021). Evaluation of Anti-SARS-Cov-2 S-RBD IgG Antibodies after COVID-19 mRNA BNT162b2 Vaccine. Diagnostics, 11.","DOI":"10.3390\/diagnostics11071135"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1016\/j.vaccine.2021.08.025","article-title":"Kinetics of SARS-CoV-2 anti-S IgG after BNT162b2 vaccination","volume":"39","author":"Grupel","year":"2021","journal-title":"Vaccine"},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Mwimanzi, F.M., Lapointe, H.R., Cheung, P.K., Sang, Y., Yaseen, F., Umviligihozo, G., Kalikawe, R., Datwani, S., Omondi, F.H., and Burns, L. (2022). Older Adults Mount Less Durable Humoral Responses to a Two-dose COVID-19 mRNA Vaccine Regimen, but Strong Initial Responses to a Third Dose. medRxiv.","DOI":"10.1101\/2022.01.06.22268745"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1473-3099(21)00681-2","article-title":"Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: Interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials","volume":"22","author":"Zeng","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e143928","DOI":"10.1172\/JCI143928","article-title":"Prolonged adaptive immune activation in COVID-19: Implications for maintenance of long-term immunity?","volume":"131","author":"Mudd","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-016-1111-6","article-title":"Adjuvant effects of a sequence-engineered mRNA vaccine: Translational profiling demonstrates similar human and murine innate response","volume":"15","author":"Edwards","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.molmed.2019.10.002","article-title":"Tailoring mRNA Vaccine to Balance Innate\/Adaptive Immune Response","volume":"26","author":"Lacroix","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/acel.12386","article-title":"Integration of \u2018omics\u2019 data in aging research: From biomarkers to systems biology","volume":"14","author":"Zierer","year":"2015","journal-title":"Aging Cell"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"E1108","DOI":"10.1073\/pnas.1525591113","article-title":"Time-coded neurotransmitter release at excitatory and inhibitory synapses","volume":"113","author":"Rodrigues","year":"2016","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"111390","DOI":"10.1016\/j.mad.2020.111390","article-title":"Why we should use topological data analysis in ageing: Towards defining the \u201ctopological shape of ageing\u201d","volume":"192","author":"Desroches","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"100998","DOI":"10.1016\/j.arr.2019.100998","article-title":"Activation of immunosuppressive network in the aging process","volume":"57","author":"Salminen","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.imlet.2020.07.004","article-title":"Homeostasis and the functional roles of CD4(+) Treg cells in aging","volume":"226","author":"Churov","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00109-020-01988-7","article-title":"Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases","volume":"99","author":"Salminen","year":"2021","journal-title":"J. Mol. Med. (Berl)"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"104297","DOI":"10.1016\/j.cellimm.2021.104297","article-title":"MDSCs, ageing and inflammageing","volume":"362","author":"Pawelec","year":"2021","journal-title":"Cell Immunol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00281-020-00818-9","article-title":"Immunosenescence is both functional\/adaptive and dysfunctional\/maladaptive","volume":"42","author":"Fulop","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.immuni.2017.03.010","article-title":"Successful and Maladaptive T Cell Aging","volume":"46","author":"Goronzy","year":"2017","journal-title":"Immunity"},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Hussien, H., Nastasa, A., Apetrii, M., Nistor, I., Petrovic, M., and Covic, A. (2021). Different aspects of frailty and COVID-19: Points to consider in the current pandemic and future ones. BMC Geriatr., 21.","DOI":"10.1186\/s12877-021-02316-5"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10522-015-9584-x","article-title":"Complex systems dynamics in aging: New evidence, continuing questions","volume":"17","author":"Cohen","year":"2016","journal-title":"Biogerontology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1006\/jtbi.2001.2431","article-title":"Complex adaptive systems, aging and longevity","volume":"213","author":"Mangel","year":"2001","journal-title":"Theor. Biol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/j.1365-2648.2005.03638.x","article-title":"Complex adaptive systems: Concept analysis","volume":"52","author":"Holden","year":"2005","journal-title":"J. Adv. Nurs."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.smim.2013.05.003","article-title":"Systems biological approaches to measure and understand vaccine immunity in humans","volume":"25","author":"Li","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.immuni.2010.10.006","article-title":"Systems vaccinology","volume":"33","author":"Pulendran","year":"2010","journal-title":"Immunity"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"a038596","DOI":"10.1101\/cshperspect.a038596","article-title":"Systems Biological Analysis of Immune Response to Influenza Vaccination","volume":"11","author":"Cortese","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-021-03791-x","article-title":"Systems vaccinology of the BNT162b2 mRNA vaccine in humans","volume":"596","author":"Arunachalam","year":"2021","journal-title":"Nature"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Tomic, A., Pollard, A., and Davis, M. (2021). Systems Immunology: Revealing Influenza Immunological Imprint. Viruses, 13.","DOI":"10.3390\/v13050948"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/intimm\/dxaa052","article-title":"Overcoming immune dysfunction in the elderly: Trained immunity as a novel approach","volume":"32","author":"Bulut","year":"2020","journal-title":"Int. Immunol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/joim.13141","article-title":"Senolytic drugs: From discovery to translation","volume":"288","author":"Kirkland","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/s41590-020-0646-0","article-title":"Blocking elevated p38 MAPK restores efferocytosis and inflammatory resolution in the elderly","volume":"21","author":"Louie","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cmet.2016.05.011","article-title":"Metformin as a Tool to Target Aging","volume":"23","author":"Barzilai","year":"2016","journal-title":"Cell Metab."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ni.3665","article-title":"A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging","volume":"18","author":"Lanna","year":"2017","journal-title":"Nat. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/4\/607\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:53:31Z","timestamp":1760136811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/4\/607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":232,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["vaccines10040607"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10040607","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]}}}