{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:47:55Z","timestamp":1786121275788,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2026B1515020044"],"award-info":[{"award-number":["2026B1515020044"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangdong Natural Science Funds for Distinguished Young Scholar","award":["26050000640"],"award-info":[{"award-number":["26050000640"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>H7N9 avian influenza virus (AIV) poses a persistent threat to poultry and public health. Despite widespread vaccination in China, rapid antigenic drift and reassortment necessitate frequent updates of vaccine strains. Phylogenetic analysis of isolates from Chinese provinces (from 2019 to 2023) showed that while surface genes diversified, the internal gene cassette remained conserved yet actively reassorted with other subtypes, suggesting internal gene compatibility may influence vaccine performance. We selected the H7N9 strain A\/chicken\/Northeast China\/19854-6\/2019 (E2), which harbors a polybasic Hemagglutinin (HA) cleavage site and predicted dual receptor-binding affinity. To enable safe vaccine development, we modified the HA cleavage site to generate a low-pathogenicity strain (E2-\u0394). Using reverse genetics, we constructed three recombinant viruses: E2-\u0394 (retaining contemporary internal genes), CVI-E2, and CVII-E2 (containing internal genes from commercially used donor strains CVI and CVII, respectively). Inactivated vaccines were evaluated in specific-pathogen-free (SPF) chickens. E2-\u0394 induced HI antibody titers comparable to those of CVI-E2 and significantly higher than those of CVII-E2, and showed modestly higher cross-reactive HI titers against some recent H7N9 variants in exploratory analyses. All vaccines provided complete homologous protection with reduced viral shedding and no clinical signs in challenge trials. Our findings suggest that internal gene backbone compatibility may influence vaccine immunogenicity. While E2-\u0394 outperformed CVII-E2, it was comparable to CVI-E2, indicating that certain traditional backbones may still be suitable for H7N9 vaccine development. This approach warrants further validation to support a refined vaccine design strategy for H7N9 and potentially other avian influenza subtypes.<\/jats:p>","DOI":"10.3390\/microorganisms14081719","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"1719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Immunogenicity of Inactivated H7N9 Avian Influenza Vaccines with Different Internal Gene Backbones"],"prefix":"10.3390","volume":"14","author":[{"given":"Yi","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqi","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Du","sequence":"additional","affiliation":[{"name":"College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liao","sequence":"additional","affiliation":[{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbao","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China"},{"name":"National Avian Influenza Para-Reference Laboratory, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory of Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou 510642, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tan, S., Sjaugi, M.F., Fong, S.C., Chong, L.C., Abd Raman, H.S., Nik Mohamed, N.E., August, J.T., and Khan, A.M. 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