{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:05:40Z","timestamp":1784027140552,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovative Drug Research and Development National Science and Technology Major Project","award":["2025ZD1804200"],"award-info":[{"award-number":["2025ZD1804200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Pandemic influenza remains a persistent global threat, and while vaccination is the primary preventive measure, conventional vaccines often induce narrow, strain-specific immunity. This study evaluated the immunogenicity, protective efficacy, and cross-protective potential of a CpG-adjuvanted trivalent inactivated influenza vaccine (CpG-TIV) administered intramuscularly at high and low doses in ferrets. Methods: Groups of influenza-seronegative ferrets received two intramuscular injections, 3 weeks apart, of high- or low-dose CpG-TIV or a commercial non-adjuvanted trivalent vaccine. Three weeks after the second immunization (Day 42), serum was obtained, and the ferrets were subsequently challenged intranasally with homologous H1N1 and influenza B viruses, as well as a heterologous drifted H3N2 strain. Clinical signs, body weight, nasal viral load, and lung histopathology were monitored following the viral challenge. Results: CpG-TIV induced significantly higher dose-dependent HI and IgG antibodies than the commercial unadjuvanted vaccine. High-dose CpG-TIV markedly reduced weight loss, clinical symptoms, nasal viral load (by up to 99%), and lung pathological damage. Notably, high-dose CpG-TIV provided significant cross-protection against heterologous H3N2, whereas the commercial vaccine showed no protective effect. At Day 42, HI GMTs in the high-dose group reached 500, 254, and 594 against H1N1, H3N2, and B strains, respectively, with a maximal 2.58 log10 reduction in H1N1 viral load. Conclusions: High-dose CpG-TIV demonstrates strong immunogenicity and robust dose-dependent homologous and heterologous cross-protection in ferrets. The combination of a CpG adjuvant and high-dose antigen broadens protection against drifted influenza viruses, overcoming the narrow coverage of conventional vaccines. These data support further clinical development of this broad-spectrum influenza vaccine candidate.<\/jats:p>","DOI":"10.3390\/vaccines14070615","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:53Z","timestamp":1784023973000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Immunogenicity and Cross-Protective Efficacy of a CpG-Adjuvanted Trivalent Inactivated Influenza Vaccine in Ferrets"],"prefix":"10.3390","volume":"14","author":[{"given":"Yanping","family":"Qiu","sequence":"first","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"He","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Wang","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiao","family":"Han","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"He","sequence":"additional","affiliation":[{"name":"Jiangsu KMQ BioTech Inc., Nantong 226000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiketus","family":"Sho","sequence":"additional","affiliation":[{"name":"Jiangsu KMQ BioTech Inc., Nantong 226000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Han","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Wu","sequence":"additional","affiliation":[{"name":"Huan Ke (Hebei) Biotechnology Co., Ltd., Shijiazhuang 050000, China"},{"name":"Huapu Shijiazhuang Pharmaceutical Co., Ltd., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev-virology-010320-044746","article-title":"Challenges of Making Effective Influenza Vaccines","volume":"7","author":"Gouma","year":"2020","journal-title":"Annu. 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