CD4+ T-cell responses directed towards A/H5N1-derived haemagglutinin peptides increase in patients with seasonal influenza A virus infection

Allen, LF; Rowntree, LC; Jenzen, M; Hagen, RR; Croft, NP; James, F; Martin, GE; Purcell, AW; Illing, PT; Tong, SYC; Cheng, AC; Kotsimbos, TC; Trubiano, JA; Kedzierska, K; Nguyen, THO

Author(s): Allen, LF; Rowntree, LC; Jenzen, M; Hagen, RR; Croft, NP; James, F; Martin, GE; Purcell, AW; Illing, PT; Tong, SYC; Cheng, AC; Kotsimbos, TC; Trubiano, JA; Kedzierska, K; Nguyen, THO;
Details: Publication Year 2026,Volume 15,Issue #8,Page e70118
Journal Title: Clinical & Translational Immunology
Publication Type: Research article
Abstract: OBJECTIVES: Recent outbreak of influenza A/H5N1 viral infections in birds and mammals worldwide prompted renewed concerns over an emerging H5N1-related influenza pandemic in the generally immunologically-naive global population. Cross-reactive CD4(+) T cells between A/H1N1 and A/H5N1 subtypes targeting internal and surface influenza proteins have been identified in humans, indicating some protection against severe and fatal A/H5N1 infection. METHODS: To detect T-cell responses towards H1 and H5 viruses, we stimulated PBMCs from patients hospitalised with seasonal influenza A viruses, alongside healthy individuals, with overlapping peptide pools spanning hemagglutinin (HA) and neuraminidase (NA) of A/Vietnam/1203/2004 (H5N1) and A/New York/18/2009 (H1N1-pdm09-like) viruses. RESULTS: Majority of acutely infected and healthy participants (100% and 75%, respectively) had detectable CD4(+) and CD8(+) T-cell responses towards H1-HA and H5-HA, whereas 30-80% of individuals had detectable H5-NA responses. H1 and H5 HA-specific CD4(+) T-cell responses highly correlated, suggesting some level of cross-reactivity between T-cell responses directed against H1 and H5 subtypes. HA-specific CD4(+) T-cell responses were increased in influenza patients compared to healthy participants. We found no differences in H1- and H5-specific T cell responses between those born pre- and post-1968, irrespective of infection status. Sequence alignment of H1 and H5 viruses identified high conservation in the HA2 stalk subunit (81.53%). CD4(+) T-cell immunity towards immunodominant HA(306-318) epitope, restricted by several HLA-DRB1 molecules, revealed limited cross-reactivity between Group 1 and Group 2 HA-subtypes. CONCLUSION: We define correlative H1- and H5-specific CD4(+) T-cell responses during seasonal influenza A virus infection, likely reflecting some level of H1/H5 T cell cross-reactivity.
Publisher: Wiley
Keywords: CD4+ T cells; H5n1; T cells; immunology; influenza virus; pandemic influenza
Department(s): Infectious Diseases
Publisher's Version: https://doi.org/10.1002/cti2.70118
Open Access at Publisher's Site: https://doi.org/10.1002/cti2.70118
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-09-03 12:44:07

Last Modified: 2026-09-03 12:44:21