Low levels of H5N1 HA and NA antibodies in the human population are boosted by seasonal A/H1N1 infection but not by A/H3N2 infection or influenza vaccination

Werner, A. P.; Schneider, C. G.; Akin, E.; Hayes, J.; Fenstermacher, K.; Rothman, R. E.; Coughlan, L.; Pekosz, A.

doi:10.1101/2025.07.13.664638

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bioRxiv · 10.1101/2025.07.13.664638

Low levels of H5N1 HA and NA antibodies in the human population are boosted by seasonal A/H1N1 infection but not by A/H3N2 infection or influenza vaccination

Werner, A. P.·Schneider, C. G.·Akin, E.·Hayes, J.·Fenstermacher, K.·Rothman, R. E.·Coughlan, L.·Pekosz, A.

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Abstract

An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus. Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody responses may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.

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Werner, A. P., Schneider, C. G., Akin, E., Hayes, J., Fenstermacher, K., Rothman, R. E., Coughlan, L., Pekosz, A.. 2025-07-16. Low levels of H5N1 HA and NA antibodies in the human population are boosted by seasonal A/H1N1 infection but not by A/H3N2 infection or influenza vaccination. https://doi.org/10.1101/2025.07.13.664638

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