Relationship between HLA and Avian Flu

The WHO estimates that roughly half the 950 documented human cases of avian influenza A(H5N1) have resulted in mortality. Recent evidence suggest the recent exposure to influenza A(H1N1)pdm09, either by prior infection or vaccination, may confer protection through cross-reactive neuraminidase (NA) inhibition antibodies. Identifying MHC Class I alleles susceptible to CD8+ T cell epitope disruption in circulating Influenza strains, such as A(H5N1), could help identify individuals at increased risk for severe disease outcomes.

Figure CD8+ epitope differences between ’24-’25 egg-based trivalent and newer Influenza A(H1N1), A(H3N2), and B/Victoria strains. Lost epitopes are defined as an HLA allele matched peptide putatively induced in the trivalent that are not found in newer strains. Conversely, gained epitopes are expressed in newer strains but not found in trivalent epitope repertoires. Created on Biorender.

Approach

we applied a validated bioinformatics pipeline to compare CD8+ epitopes between seven highly pathogenic A(H5N1) strains sequenced between February 2023 and December 2024 and the A(H1N1)pdm09 neuraminidase in the 2024-2025 trivalent influenza vaccine.
This work was an application our of COVD-19 research.

Key Findings

Vaccinated individuals carrying HLA-A*31:01, -A*33:01, -A*68:01, and -B*07:02, estimated to affect roughly 5- 12% of the population, may be at increased risk of severe disease.
Across all A(H5N1) variants, 51% (166/327) of N1 NA and 74% (279/391) H5 HA CD8+ epitopes were conserved.
All alleles analyzed had at least one epitope conserved in both proteins, except HLA-B*44:02 and -B*44:03, which had no putative NA epitopes conserved.
These findings suggest that the 2024-2025 northern hemisphere trivalent influenza egg-based vaccine 90 may provide cross protection against HPAI A(H5N1) for most of the population through conserved N1 NA CD8+ epitopes.

Outputs

manuscript in progress