{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:07:48Z","timestamp":1783462068775,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study investigates the immunoenhancing effects of the probiotic <jats:italic>Lactobacillus brevis<\/jats:italic> ZG2488 on an adenovirus-vectored SARS-CoV-2 vaccine (AdC68-Delta-S) in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were administered ZG2488 in combination with AdC68-Delta-S. Immune responses were evaluated by measuring SARS-CoV-2-specific IgG in bronchoalveolar lavage fluid (BALF), IFN-\u03b3 secretion by splenocytes, and transcriptomic and CIBERSORT analyses of splenic immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ZG2488 intervention significantly enhanced local mucosal humoral immunity in the respiratory tract (increased SARS-CoV-2-specific IgG in BALF) and systemic Th1 cellular immunity (increased IFN-\u03b3 secretion by splenocytes). Transcriptomic analysis revealed upregulation of the JAK-STAT signaling pathway, antigen processing and presentation pathways, and pro-inflammatory pathways (IL-17\/TNF\/NLR\/PI3K-Akt), alongside downregulation of hyperinflammation-associated pathways. CIBERSORT analysis showed that ZG2488 reshaped splenic immune cell composition, increasing memory CD4<jats:sup>+<\/jats:sup> T cells, Th1 cells, and dendritic cells (DCs), while decreasing macrophages, follicular helper T (Tfh) cells, monocytes, and \u03b3\u03b4 T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings demonstrate that L. brevis ZG2488 enhances the immune response to the SARS-CoV-2 vaccine through synergistic and multi-mechanistic actions, supporting its potential as a probiotic adjuvant strategy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1655383","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:28:29Z","timestamp":1760419709000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunomodulatory effects of probiotic Lactobacillus brevis ZG2488 on SARS-CoV-2 vaccine responses in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengshan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e166","DOI":"10.1136\/annrheumdis-2019-215174","article-title":"Effectiveness of influenza vaccine in TNF inhibitors treated patients: comment on the article by Burmester et al","volume":"79","author":"Adami","year":"2020","journal-title":"Ann. 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