CD8 T cell epitope conservation in emerging H5N1 viruses suggests global protection.

Objectives: The recent H5N1 avian influenza outbreak in the USA has sparked fresh fears of avian viruses causing the next pandemic. To date, the H5N1 (clade 2.3.4.4b) outbreak in cattle has spread across several states in the USA, with several humans infected following exposure to cows. This H5N1 clade is also reportedly circulating across Europe, Africa and South America. H5N1 was also detected in a child returning to Australia following travel in India where H5N1 (clade 2.3.2.1a) is also reported to be circulating. There are no licenced vaccines against H5N1 avian influenza viruses for humans. Current vaccines aim to protect against seasonal H1N1 and H3N2 variants are unlikely to provide much protection against the different H5, or other avian viruses. CD8 T cells are known to provide protection against influenza infection, enhancing viral control and decreasing disease severity.

Methods: We recently compiled and published a list of the known immunogenic influenza-derived CD8 T cell epitopes restricted to the most prevalent 10 HLA-A, -B and -C molecules worldwide. We assessed the conservation of a curated list of these influenza A virus-derived CD8 T cell epitopes in H5N1 viruses' sequences at the heart of the outbreak.

Results: We identified that > 64% of the CD8 T cell epitopes are highly conserved (> 90% sequence identity) in the H5N1 viruses, with 60% (18/30) of the most prevalent HLA-I molecules have at least one immunogenic CD8 T cell epitope conserved in H5N1 viruses. Together these HLA-I molecules with conserved epitopes have a cumulative total of > 100% global coverage. Epitopes derived from the NP, M1, PB2, NS1 and PB1 proteins displayed the highest level of conservation.

Conclusions: Together, this analysis highlights that globally there is the potential for T cell cross-recognition against the H5N1 viruses that may provide some protection in humans towards the current avian flu outbreak.