{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:57Z","timestamp":1789016877393,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"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":["2023A1515011767"],"award-info":[{"award-number":["2023A1515011767"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Projects in Guangzhou","award":["2024A04J4015"],"award-info":[{"award-number":["2024A04J4015"]}]},{"name":"Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences","award":["2022-RC310-02"],"award-info":[{"award-number":["2022-RC310-02"]}]},{"award":["2022-RC310-02"],"award-info":[{"award-number":["2022-RC310-02"]}],"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-2-001"],"award-info":[{"award-number":["2023-I2M-2-001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502213"],"award-info":[{"award-number":["82502213"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82502213"],"award-info":[{"award-number":["82502213"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: Influenza remains a significant global public health threat, causing substantial morbidity and mortality worldwide. While vaccination serves as the best preventive strategy, considerable interindividual variability in vaccine-induced immune responses persists. The ZBTB46 rs2281929 polymorphism (c.A31G; p.T11A; ACG&gt;GCG), which corresponds to the evolutionarily conserved mouse mutation Zbtb46T11A (c.A31G; ACT&gt;GCT), has been associated with enhanced antibody responses to influenza vaccination in humans, though its functional mechanisms remain unknown. This study aimed to investigate how this mutation affects influenza vaccine immunogenicity using a knock-in mouse model. Methods: A Zbtb46T11A knock-in mouse model was generated using CRISPR\/Cas9 technology. Homozygous (HO) and wild-type (WT) mice were immunized with a quadrivalent influenza vaccine in a prime-boost regimen. Humoral immune responses were assessed by Enzyme-linked immunosorbent assay, hemagglutination inhibition (HI), and microneutralization (MN) assays. Antibody-secreting cells (ASCs) were quantified by Enzyme-linked immunospot assays. Germinal center B cells, plasma cells, plasmablast cells, conventional dendritic cell (cDC) subsets, and T helper (Th) cells were analyzed by flow cytometry. Statistical comparisons were performed using a two-sample t-test. Results: The Zbtb46T11A mutation did not alter Zbtb46 protein expression or its abundance in cDCs. Following vaccination, HO mice exhibited significantly enhanced humoral responses, including higher HA-specific IgG titers, HI and MN antibody levels, and increased numbers of ASCs. Flow cytometry revealed elevated proportions of germinal center B cells and plasma cells in HO mice. Furthermore, HO mice showed a selective expansion of type 1 cDCs (cDC1s) and a concomitant increase in Th1 cell frequencies and IFN-\u03b3-secreting cells, while cDC2 proportions and Th2 responses remained unchanged. Conclusions: The Zbtb46T11A mutation is associated with enhanced influenza vaccine immunogenicity, concomitant with increased cDC1 proportions, Th1 polarization, and germinal center-dependent humoral immunity. These observed associations suggest a candidate mechanism whereby Zbtb46 modulation may shape adaptive immunity, though further functional studies are required to establish causality. These findings provide insights into host genetic variation in vaccine responsiveness and may inform personalized vaccination strategies.<\/jats:p>","DOI":"10.3390\/biology15171558","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zbtb46T11A Mutation Is Associated with Enhanced Influenza Vaccine Immunogenicity and Altered cDC1 Proportions in Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7481-1327","authenticated-orcid":false,"given":"Yifan","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yuxuan","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Qiuyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hospital Administration, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Shumiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Qian","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Lifang","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Ruiqi","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Simin","family":"Wen","sequence":"additional","affiliation":[{"name":"Guangzhou First People\u2019s Hospital, Guangzhou 510180, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9279-0916","authenticated-orcid":false,"given":"Yuelong","family":"Shu","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7305a1","article-title":"Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices\u2014United States, 2024-25 Influenza Season","volume":"73","author":"Grohskopf","year":"2024","journal-title":"MMWR Recomm. 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