CD4
+
T‐cell responses directed towards A/H5N1‐derived haemagglutinin peptides increase in patients with seasonal influenza A virus infection
Lilith F Allen, Louise C Rowntree, Mitchell Jenzen, Ruth R Hagen, Nathan P Croft, Fiona James, Genevieve E Martin, Anthony W Purcell, Patricia T Illing, Steven Y C Tong, Allen C Cheng, Tom C Kotsimbos, Jason A Trubiano, Katherine Kedzierska, Thi H O Nguyen 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.