Cross-Reactive Antibody Responses to Emerging Bovine H5N1 Clade 2.3.4.4b Following Seasonal Influenza Vaccination: Implications for Pandemic Preparedness

Seasonal influenza vaccination is associated with cross-reactive HA-binding antibodies against bovine H5N1 clade 2.3.4.4b in a substantial proportion of individuals, with responses increasing with age. This suggests pre-existing immunity from vaccination or prior exposures may influence responses to this zoonotic threat. However, the functional neutralizing capacity and protective efficacy of these antibodies are unproven. These findings highlight the potential immunological footprint of current vaccines against emerging strains and support further investigation into cross-protection. They also reinforce the importance of conserved HA epitopes as targets for next-generation universal influenza vaccines.