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Flavivirus vaccines are believed to confer protection primarily through antibody responses; however, the role of T cells in vaccine immunity remains less explored despite demonstrated contribution in the response to natural infection. This review examines T cell responses induced by licensed or developing flavivirus vaccines, their contribution to protection, and key findings highlighting the importance of cellular immunity. We discuss the role of memory T cells, including CD4+ and CD8+ subsets, in flavivirus vaccine\u2010induced immunity and compare the immunogenicity of live attenuated versus inactivated vaccines. We also discuss the significance of T cell immunity, cross\u2010reactivity, and vaccine platform design in shaping durable and broad protection. Additionally, we broaden the discussion toward other human RNA viruses, including the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102). A better understanding of the role of T cell immunity will be essential for optimizing the use of current flavivirus vaccines and developing next\u2010generation approaches capable of providing long\u2010lasting immunity against emerging and re\u2010emerging flavivirus threats.<\/jats:p>","DOI":"10.1002\/eji.70027","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T04:48:47Z","timestamp":1755492527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human T Cell Responses to Flavivirus Vaccines"],"prefix":"10.1002","volume":"55","author":[{"given":"David","family":"Wullimann","sequence":"first","affiliation":[{"name":"Center For Infectious Medicine Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Gustaf","family":"Ljunggren","sequence":"additional","affiliation":[{"name":"Center For Infectious Medicine Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705\u2010023\u201005835\u20101"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1458166"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564\u2010020\u20100714\u20100"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2017.07.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1081107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000718"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985\u2010021\u201001611\u20102"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201092403\u20109"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.02.023"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985\u2010016\u20100590\u20107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.04.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.975398"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010018\u20100210\u20103"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000707\u20102"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1092"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-79058-1.00002-5"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005263"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072290"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541\u2010020\u20100205\u20106"},{"key":"e_1_2_10_21_1","first-page":"895","article-title":"Persistence of Neutralizing Antibody 30\u201335 Years After Immunization with 17D Yellow Fever Vaccine","volume":"59","author":"Poland J. 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