{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T03:56:17Z","timestamp":1783828577945,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianjin Key Science and Technology Support Project","award":["24YFZCSN00180"],"award-info":[{"award-number":["24YFZCSN00180"]}]},{"name":"Shandong Key Science and Technology Project","award":["2025TSGCCZZB015"],"award-info":[{"award-number":["2025TSGCCZZB015"]}]},{"name":"Tianjin Municipal Major Science and Technology Projects and Engineering","award":["25ZXCKQY00020"],"award-info":[{"award-number":["25ZXCKQY00020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, we generated high-affinity heavy-chain variable domain (VHH) nanobodies from na\u00efve alpaca\/camelid VHH libraries using phage display combined with H9N2 influenza A virus (IAV)-infected Madin-Darby Canine Kidney (MDCK) cells. Based on binding affinity and neutralization potential, we identified seven hemagglutinin (HA)-specific and two neuraminidase (NA)-specific VHHs. Molecular docking predicted the interaction sites of HA-specific VHHs (L1-2, L1-4, A5) and NA-specific VHHs (L1-3, L2-2), providing mechanistic insights. Notably, the three HA-specific VHHs (L1-2, L1-4, A5) showed cross-reactivity to representative HA subtypes (H1, H3, and influenza B), indicating recognition of conserved epitopes across divergent influenza strains. For the first time, these camelid nanobodies were fused to the chicken IgY Fc domain, and the expression cassette was integrated into the Saccharomyces cerevisiae genome, achieving a secretion yield of 15\u201320 mg\/L of VHH-Fc antibodies. Experimental validation confirmed that the three HA-specific VHHs-Fc constructs effectively blocked viral infection, while the two NA-specific VHH-Fc constructs (L1-3, L2-2) inhibited NA activity, demonstrating the functional efficacy of the yeast-secreted VHH\u2013IgY Fc platform. This novel IgY Fc fusion approach offers a scalable platform with enhanced stability, extended circulation potential, and applicability in poultry.<\/jats:p>","DOI":"10.3390\/cells15080655","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:49:44Z","timestamp":1775641784000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Phage Display to Yeast Secretion: Developing Fc-Fused Nanobodies Against Influenza Virus"],"prefix":"10.3390","volume":"15","author":[{"given":"Mei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8238-6708","authenticated-orcid":false,"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Zoo, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-0379","authenticated-orcid":false,"given":"Lilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-533X","authenticated-orcid":false,"given":"Jinhai","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gongal, G., Rahman, H., Thakuri, K.C., and Vijayalakshmy, K. 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