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We found that milk pasteurization fully inactivated pandemic H1N1 and bovine H5N1 influenza viruses yet preserved hemagglutinin (HA) protein integrity. In mice, repeated oral exposure to inactivated virus did not alter mortality after H5N1 virus challenge. Preliminary data showed that na\u00efve mice exposed to improperly pasteurized milk containing live H5N1 virus developed lethal infection, whereas prior H1N1 infection conferred protection. Mice with preexisting H1N1 immunity remained protected when challenged with bovine H5N1 virus after exposure to H5N1 pasteurized in milk. These findings suggest that pasteurized milk containing inactivated H5N1 virus poses minimal health risks.<\/jats:p>","DOI":"10.1126\/sciadv.aeb3906","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:58:32Z","timestamp":1758909512000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Repeated oral exposure to H5N1 influenza virus in pasteurized milk does not cause adverse responses to subsequent influenza infection"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-2608","authenticated-orcid":true,"given":"Pamela H.","family":"Brigleb","sequence":"first","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ericka Kirkpatrick","family":"Roubidoux","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8429-0066","authenticated-orcid":true,"given":"Lauren","family":"Lazure","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandi","family":"Livingston","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-9177","authenticated-orcid":true,"given":"Victoria A.","family":"Meliopoulos","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-4188","authenticated-orcid":true,"given":"Bridgett","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1686-0147","authenticated-orcid":true,"given":"Tyler","family":"Ripperger","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-2208","authenticated-orcid":true,"given":"Dorothea R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoyuan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2021-727X","authenticated-orcid":true,"given":"Stacey","family":"Schultz-Cherry","sequence":"additional","affiliation":[{"name":"Department of Host Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00868-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01087-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07849-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3007.240508"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","unstructured":"X. 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Schultz-Cherry Immune history modifies disease severity to HPAI H5N1 clade 2.3.4.4b viral challenge. bioRxiv 2024.10.23.619695 [Preprint] (2024). https:\/\/doi.org\/10.1101\/2024.10.23.619695.","DOI":"10.1101\/2024.10.23.619695"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.4.937-943.1999"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.13.35"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeb3906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:58:35Z","timestamp":1758909515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeb3906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":51,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,9,26]]}},"alternative-id":["10.1126\/sciadv.aeb3906"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeb3906","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeb3906"}}