{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:26:21Z","timestamp":1780093581423,"version":"3.54.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emerging threats such as highly pathogenic influenza strains like H5N1 emphasize the need for vaccines that induce cross-reactive immunity against conserved epitopes. Existing influenza vaccines primarily elicit strain-specific responses, leaving gaps in protection against pandemic subtypes. This study aimed to evaluate T cell responses to seasonal influenza A and H5N1 and compare them to SARS-CoV-2 specific T cell responses to understand differences shaped by distinct exposure histories and vaccination strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>T cell responses were assessed in 41 laboratory workers who received annual seasonal influenza vaccines using ELISpot to quantify responses to peptide pools derived from influenza (H1N1 hemagglutinin [HA], H3N2 HA, H5N1 HA, matrix protein 1 [MP1], nucleoprotein [NP]) and SARS-CoV-2 (spike [S2S], nucleocapsid [S2N]). Ten-day expansion assays were used to evaluate functional cross-reactivity between H1, H3, and H5 HA. Intracellular cytokine staining was performed to assess antigen-specific T cell functionality. We used the IFN-\u03b3 ELISpot assay and intracellular cytokine staining to evaluate T cell responses to H5N1 HA peptides and assessed cross-reactivity and functional similarity in H1N1 HA-expanded cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The percentage of individuals with effector T cell responses to influenza peptide pools, was markedly lower than the percentage of individuals with S2S-specific T cells. However, HA-specific memory cells that cross-recognized H1, H3, and H5 HA were present in many individuals. T cells expanded with H1 or H5 HA proteins cross-recognized homologous epitopes in the 2 proteins and cytokine production profiles were comparable between H1- and H5-expanded T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results highlight the potential for influenza vaccines to elicit cross-reactive immunity against H5N1 viruses. These findings also demonstrate differences between T cell responses to influenza and SARS-CoV-2, highlighting distinct immune profiles that could inform future vaccine strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1718805","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:44:50Z","timestamp":1766040290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["T cell immunity to seasonal Influenza A and H5N1 viruses in laboratory workers receiving annual seasonal Influenza vaccines"],"prefix":"10.3389","volume":"16","author":[{"given":"Joel","family":"Sop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler 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