Pre-existing cross-subtype serological responses against H5Nx in health care workers

A rise in cases of highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b in humans has been reported since 2023. Although influenza seasonal vaccination (H1N1/H3N2) was shown to be effective against cases of reinfection with endemic influenza A viruses (IAVs), its capacity to elicit cross-reactive antibodies against (H5N1) remains unclear. Here, we measured vaccine-elicited antibody responses against seasonal (H1N1/H3N2) and various avian subtypes A (H5Nx) using plasma samples from the CRCHUM Health Care Workers cohort in Montreal, Canada, during the 2024 influenza seasonal vaccination. The capacity of their plasma to recognize hemagglutinin (HA) and neuraminidase (NA) antigens from ten influenza strains was measured. Their neutralizing activity, as well as their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against cells stably expressing HA and NA, was measured. Overall, seasonal vaccination against H1N1/H3N2 elicited antibodies able to recognize several HA and NA, and in some individuals, this translated to increased neutralization and ADCC activity, including against H5Nx. This study provides insightful information on how vaccination shapes cross-reactive antibody responses against avian H5Nx.