Long-term Dynamics and Cross-reactivity of Neuraminidase Inhibition Antibodies in Mallards following Infection with High Pathogenicity Avian Influenza Viruses

Genetically diverse H5Nx high pathogenicity avian influenza viruses (HPAIVs) have circulated globally among wild and domestic birds and are largely disseminated by migratory waterfowl such as mallards. Birds that survive infection acquire immunity, which influences the course of reinfection. To clarify how HPAIVs evade host immunity in carriers and spread through them, we investigated serum antibody responses against neuraminidase (NA) in mallards experimentally infected with H5N1 and H5N8 HPAIVs isolated in Japan. Despite a single low-dose inoculation, NA inhibition (NI) antibodies against homologous strains emerged early and remained detectable for approximately three months. These NI antibodies exhibited pronounced cross-reactivity among viruses sharing the same NA subtype. Our findings provide new insights into the long-term dynamics of NI antibodies in mallards and their potential role, along with hemagglutinin inhibition and neutralization antibodies, in protecting against HPAIV reinfection.