{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:41:38Z","timestamp":1776055298428,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Older people mount poorer adaptive immune responses to mRNA vaccines, leaving them more vulnerable to infection with SARS\u2010CoV\u20102. To design better mRNA vaccines for older people, we need to understand how aging alters mechanisms of adjuvancy that shape immunogenicity. To first define age\u2010related changes in immunogenicity, we vaccinated young (&lt;\u20095\u2009months old) and aged (&gt;\u200918\u2009months old) C57BL\/6 mice with an mRNA vaccine encoding the SARS\u2010CoV\u20102 spike protein. T\u00a0cell responses were markedly reduced in aged mice at peak and memory timepoints, using intracellular cytokine staining or activation\u2010induced marker assays. Spike and receptor\u2010binding domain binding and neutralizing antibody titers were also markedly reduced in aged mice, consistent with deficits seen in older humans. To define age\u2010related changes in adjuvancy mechanisms, we vaccinated young and aged mice with mRNA vaccines loaded with DiD lipid dye or mScarlet mRNA, then tracked dendritic cell (DC) numbers, phenotype, vaccine uptake, antigen expression, and activation, as well as local and systemic cytokine production. DC numbers in the draining lymph nodes (dLN) were dramatically reduced before and early after vaccination in aged compared to young mice, with delayed recruitment of DCs to the dLN. Vaccine uptake was not impacted by age, but the frequency of DCs expressing antigen increased with age and DC activation decreased with age. Aging accelerated the expression of some cytokines (IL\u20101\u03b1, IL\u20106), while delaying others (IFN\u03b3, MCP\u20101) in dLNs and sera. This illustrates that aging impairs multiple adjuvancy mechanisms but mRNA vaccine strategies that address these age\u2010related deficits could improve responses in older people.<\/jats:p>","DOI":"10.1111\/imcb.70102","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:40:50Z","timestamp":1773358850000},"page":"400-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>Age\u2010related differences in mRNA<\/scp>\n                    vaccine immunogenicity and adjuvancy"],"prefix":"10.1111","volume":"104","author":[{"given":"Shivali Savita","family":"Chinni","sequence":"first","affiliation":[{"name":"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) University  Bundoora VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma S","family":"Trollope","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) University  Bundoora VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Leung","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) University  Bundoora VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan L","family":"McQualter","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences Royal Melbourne Institute of Technology (RMIT) University  Bundoora VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chee Wah","family":"Tan","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore"},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linfa","family":"Wang","sequence":"additional","affiliation":[{"name":"Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Lim","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences (MIPS) Monash University  Parkville VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam K","family":"Wheatley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A","family":"Juno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC Australia"},{"name":"Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School Monash University  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hareth A","family":"Al\u2010Wassiti","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences (MIPS) Monash University  Parkville VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin W","family":"Pouton","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences (MIPS) Monash University  Parkville VIC 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