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Adv."],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:p>Highly pathogenic avian influenza (HPAI) H5N1 virus spillover into dairy cows represents the emergence of a mammalian host capable of sustaining a panzootic and creates a transmission pathway to humans. HPAI research involving dairy cows is constrained by the space requirements needed to house large animals in high biocontainment. A small ruminant model would enable larger sample sizes while reducing costs, improving safety, and lowering logistical barriers to conduct research. Here, we establish dairy goats as a model for HPAI mammary infection. Intramammary inoculation with HPAI H5N1 genotype D1.1 and genotype B3.13 resulted in acute mastitis, decreased milk yield, and high virus shedding in milk. Parenteral vaccination with an inactivated virus induced antigen-specific antibodies in blood and milk, reduced clinical disease, limited virus shedding in milk, and mitigated milk production losses. HPAI H5N1 disease dynamics in dairy cows can be recapitulated in dairy goats, providing a relevant model for investigating pathogenesis and for supporting the development of control strategies.<\/jats:p>","DOI":"10.1126\/sciadv.aei3111","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:58:53Z","timestamp":1792173533000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A caprine mammary infection model for highly pathogenic avian influenza H5N1"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-5637","authenticated-orcid":true,"given":"Lauren","family":"Aubrey","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."},{"name":"Vaccinology and Immunotherapeutic Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Berube","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Swan","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-3987","authenticated-orcid":true,"given":"M. Afzal","family":"Javed","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5088-0646","authenticated-orcid":true,"given":"Claire","family":"Bertens","sequence":"additional","affiliation":[{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Scruten","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Stevens","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Norleen","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla","family":"Cutts","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4879-5442","authenticated-orcid":true,"given":"Yanyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Prairie Diagnostic Services (PDS) Inc., Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5958-3525","authenticated-orcid":true,"given":"Yohannes","family":"Berhane","sequence":"additional","affiliation":[{"name":"National Centre for Foreign Animal Disease, Winnipeg, Manitoba, Canada."},{"name":"Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada."},{"name":"Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Warner","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."},{"name":"Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4551-9386","authenticated-orcid":true,"given":"Antonio","family":"Facciuolo","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."},{"name":"Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4706-1543","authenticated-orcid":true,"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."},{"name":"Vaccinology and Immunotherapeutic Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."},{"name":"Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08054-z"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38415-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51490-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3006.231033"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41182-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq0900"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3007.240717"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11060561"},{"key":"e_1_3_2_10_2","unstructured":"\u201cAPHIS confirms D1.1 genotype in dairy cattle in Nevada\u201d (Animal and Plant Health Inspection Service US Department of Agriculture 2025); www.aphis.usda.gov\/news\/program-update\/aphis-confirms-d11-genotype-dairy-cattle-nevada-0."},{"key":"e_1_3_2_11_2","unstructured":"\u201cUpdate: Genetic sequencing results for Wisconsin dairy herd detection of highly pathogenic avian influenza\u201d (Animal and Plant Health Inspection Service US Department of Agriculture 2025); www.aphis.usda.gov\/news\/agency-announcements\/update-genetic-sequencing-results-wisconsin-dairy-herd-detection-highly."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44298-025-00138-5"},{"key":"e_1_3_2_13_2","unstructured":"\u201cHPAI confirmed cases in livestock\u201d (Animal and Plant Health Inspection Service US Department of Agriculture USDA 2024); www.aphis.usda.gov\/livestock-poultry-disease\/avian\/avian-influenza\/hpai-detections\/hpai-confirmed-cases-livestock."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07849-4"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61553-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-73490-6"},{"key":"e_1_3_2_17_2","unstructured":"\u201cA(H5) bird flu: Current situation\u201d (US Centers for Disease Control and Prevention 2026); www.cdc.gov\/bird-flu\/situation-summary\/index.html."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2414610"},{"key":"e_1_3_2_19_2","unstructured":"\u201cInfluenza A virus subtypes H5 H7 and H9: Infectious substances pathogen safety data sheet\u201d (Government of Canada 2023); www.canada.ca\/en\/public-health\/services\/laboratory-biosafety-biosecurity\/pathogen-safety-data-sheets-risk-assessment\/influenza-a-virus-subtypes-h5-h7-h9.html."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08166-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-01998-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"K. S. Davila M. W. Brand E. Putz P. Boggiatto H. Seger A. Baker T. Anderson C. Hutter A. Buckley A. V. Plaats R. Friedrich P. Gordon B. Arruda C. Souza B. Davidson M. Palmer Inoculation with highly pathogenic avian influenza H5N1 genotype D1.1 in na\u00efve dairy cows and dairy cows previously exposed to genotype B3.13 (2025); www.researchsquare.com\/article\/rs-8339573\/v1.","DOI":"10.21203\/rs.3.rs-8339573\/v1"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","unstructured":"N. N. Tarbuck H. J. Cochran E. A. Martin M. Liu K. S. Kulchytsky W. M. Leone R. J. Webby C. J. Warren A. S. Bowman Natural H5N1 immunity in dairy cows is durable and cross-protective but non-sterilizing. bioRxiv 697911 [Preprint] (2026); https:\/\/doi.org\/10.64898\/2026.01.06.697911.","DOI":"10.64898\/2026.01.06.697911"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020296"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.5713\/ab.24.0560"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116346"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","unstructured":"J. Butler P. Rainard J. Lippolis H. Salmon I. Kacskovics in Mucosal Immunology (Elsevier 2015) pp. 2269\u20132306.","DOI":"10.1016\/B978-0-12-415847-4.00116-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0720(15)30003-7"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2021-20434"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.854890"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaf262"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.1104"},{"key":"e_1_3_2_33_2","unstructured":"\u201cEpidemiological Bulletin: 2024 Highly pathogenic avian influenza (H5N1) livestock event \u2013 Nevada and Arizona H5N1 D1.1 H\u201d (US Department of Agriculture 2025); www.aphis.usda.gov\/sites\/default\/files\/20250611-epi-brief-nevada-arizona-h5n1-dairy.pdf."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00993-06"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002186"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222213"},{"key":"e_1_3_2_37_2","first-page":"e03479","article-title":"Targets of influenza human T-cell response are mostly conserved in H5N1","volume":"16","author":"Sidney J.","year":"2024","unstructured":"J. Sidney, A.-R. Kim, R. D. de Vries, B. Peters, P. S. Meade, F. Krammer, A. Grifoni, A. Sette, Targets of influenza human T-cell response are mostly conserved in H5N1. mBio 16, e03479\u2013e03424 (2024).","journal-title":"mBio"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00268-2"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02144-25"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02356-24"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.01.051"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aei3111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:59:49Z","timestamp":1792173589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aei3111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":40,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026,10,16]]}},"alternative-id":["10.1126\/sciadv.aei3111"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aei3111","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaei3111"}}