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Pre-existing 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 titers were detected in a cohort of 73 individuals. Conversely, bovine A\/H5N1 NA-binding and neuraminidase-inhibiting antibody titers 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 titers may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>A\/H5N1 influenza A viruses continue to pose a pandemic threat to humans. Recent infection of dairy cattle and poultry with A\/H5N1 in the USA has magnified that concern. We determined the level of antibodies that recognize A\/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins in a population in Baltimore, MD. We show that while low levels of H5 HA-binding and A\/H5N1-neutralizing antibodies are present, there is a significantly stronger recognition of bovine N1 NA. Vaccines that target the N1 NA protein may induce protective antibody responses in humans due to the presence of cross-reactive human N1 NA antibodies.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02145-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T12:00:15Z","timestamp":1761912015000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Low levels of influenza H5N1 HA and NA antibodies in the human population are boosted by seasonal H1N1 infection but not by H3N2 infection or influenza vaccination"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-6830","authenticated-orcid":false,"given":"Anne P.","family":"Werner","sequence":"first","affiliation":[{"name":"W. 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