{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:54:51Z","timestamp":1781844891619,"version":"3.54.5"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01AI124299"],"award-info":[{"award-number":["U01AI124299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Highly pathogenic avian influenza (HPAI) is a lethal disease of poultry that has recently spilled over into mammals, including dairy cattle and humans, heightening concerns for livestock health, food security, and pandemic emergence. While vaccines that induce neutralizing antibodies against hemagglutinin and neuraminidase provide strain-specific protection, durable cross-subtype immunity requires T-cell responses targeting conserved internal antigens such as nucleoprotein (NP). To leverage these conserved targets, we utilized a previously engineered mosaic nucleoprotein (MNP) incorporating T-cell epitopes from thousands of influenza A virus (IAV) strains, conferring broad protection against epidemic (H3N2) and pandemic (H1N1) IAV in mice. Here, we tested whether precision adjuvancy could differentially imprint adaptive immunity to MNP in cattle. Combination formulations paired the carbomer-based nano-emulsion Adjuplex (ADJ) with either a STING agonist (cyclic dinucleotides; CdN) or a TLR4 agonist (glucopyranosyl lipid A; GLA) to program distinct inflammatory milieus. Both formulations elicited circulating IFN-\u03b3\u2013producing T cell responses and NP-specific antibodies in serum and milk. However, STING activation via CdN generated more potent and consistent cellular and humoral immunity than TLR4 engagement. These data demonstrate that selective activation of innate sensing pathways functionally imprints adaptive immune magnitude and quality in a large animal host. By advancing a broadly protective, T-cell-focused vaccine strategy in cattle, this work supports a One Health framework to mitigate H5N1 transmission risk at the human\u2013animal interface.<\/jats:p>","DOI":"10.3390\/v18060670","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:46:28Z","timestamp":1781588788000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Innate Pathway Selection Modulates Antibody and T-Cell Responses to Mosaic Influenza Nucleoprotein in Cattle"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9217-3190","authenticated-orcid":false,"given":"Clara","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5836","authenticated-orcid":false,"given":"Thomas","family":"Cleven","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1907-9801","authenticated-orcid":false,"given":"Marlee","family":"Henige","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Wisconsin Veterinary Diagnostic Laboratory, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Maroney","sequence":"additional","affiliation":[{"name":"Research Animal Resources and Compliance, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lautaro","family":"Rostoll-Cangiano","sequence":"additional","affiliation":[{"name":"Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doerte","family":"Doepfer","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1794-3358","authenticated-orcid":false,"given":"Marulasiddappa","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","unstructured":"Food and Agriculture Organization of the United Nations (2026, February 13). 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Immunol., 10.","DOI":"10.3389\/fimmu.2019.01400"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:33:06Z","timestamp":1781843586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,13]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["v18060670"],"URL":"https:\/\/doi.org\/10.3390\/v18060670","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,13]]}}}