ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicExploring Immune Evasion and Vaccine Strategies in Host-Pathogen InteractionsView all 6 articles
T cell immunity to seasonal Influenza A and H5N1 viruses in laboratory workers receiving annual seasonal Influenza vaccines
Provisionally accepted
- Johns Hopkins Medicine, Baltimore, United States
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Background 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. Methods 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-γ 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. Results 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. Conclusion 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.
Keywords: H5N1 (Avian influenza), T cell epitope, Sars - cov - 2, T cell, Vaccine
Received: 04 Oct 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Sop, Beckey, Gutierrez, Zhang, Gebo, Smith and Blankson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joel Blankson
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