Publications

Objectives: Immunisation remains the most cost-effective mechanism to combat influenza infection and is widely employed against seasonal influenza viruses. Zoonotic transmission of avian influenza A viruses represents a significant threat to human health given the lack of population-level immunity. Therefore, there is a need to better understand pre-existing cross-reactive human immunity against avian influenza strains, as highlighted by the recent global spread of avian H5Nx clade 2.3.4.4b variants.

Methods: Here, we quantified the frequencies and specificities of B and T cells recognising avian hemagglutinin (HA) within unexposed adults and characterised the ability of seasonal immunisation to boost cross-reactive immune responses to H5Nx strains, including from clade 2.3.4.4b.

Results: Low but detectable serum antibody titres against H5 and H7 avian influenza HA were observed in donors. The frequency of memory B cells with cross-reactive recognition of H5 and H7 HA was below 0.13% and two- to five-fold lower than populations of seasonal HA-specific B cells. Boosting of B-cell responses against clade 2.3.4.4b H5Nx HA following seasonal immunisation was sporadic with only three of 19 individuals showing an increased population of probe-positive cells. Cross-reactive B cells generally expressed immunoglobulins drawn from variable heavy chain genes associated with HA stem recognition. CD4+ T-cell responses towards H5 HA were weakly boosted with little increase in circulating T follicular helper cell populations.

Conclusion: These findings highlight the need for avian influenza-specific vaccine products to bolster immunity in human populations. Such vaccines could aid pre-pandemic preparedness by expanding baseline frequencies of avian influenza-specific memory lymphocytes.