{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T01:56:39Z","timestamp":1772848599994,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["20K09717"],"award-info":[{"award-number":["20K09717"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Acute otitis media is a common pediatric infection caused primarily by nontypeable Haemophilus influenzae. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1\/PD-L1 pathway has been extensively studied for its role in tumor immunity, its impact on mucosal immunity, particularly in vaccine responses, is unclear. Methods: BALB\/c mice were intranasally immunized with nontypeable H. influenzae outer membrane protein and treated with anti-PD-L1 antibodies. Immune responses were evaluated in middle ear mucosa (MEM), the cervical lymph node, and the spleen using an enzyme-linked immunosorbent assay, an enzyme-linked immunospot assay, and flow cytometry. The effects on CD4+ T cells, T follicular helper (Tfh) cells, and B-cell differentiation were analyzed. Results: Anti-PD-L1 antibody treatment increased CD3+CD4+CD185+ (CXCR5+) Tfh cells in MEM, which play a crucial role in supporting B-cell activation and antibody production. This correlated with a significant increase in IgA- and IgG-producing cells in MEM, which enhanced local bacterial clearance. Although B-cell activation and differentiation into plasmablasts were observed in MEM, no significant changes were noted in the cervical lymph node and spleen, suggesting a localized enhancement of mucosal immunity. Conclusions: Anti-PD-L1 antibodies promoted Tfh cell expansion and B-cell differentiation in MEM, leading to enhanced antibody production and improved bacterial clearance. These findings suggest that PD-L1 blockade can potentiate mucosal vaccine-induced immunity by strengthening local humoral responses. This supports its potential application in developing intranasal vaccines for acute otitis media.<\/jats:p>","DOI":"10.3390\/vaccines13030313","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T10:16:45Z","timestamp":1741861005000},"page":"313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of Haemophilus influenzae Outer Membrane Protein"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-6927","authenticated-orcid":false,"given":"Kazuhiro","family":"Yoshinaga","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8579-5065","authenticated-orcid":false,"given":"Takashi","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-3020","authenticated-orcid":false,"given":"Shingo","family":"Umemoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-8083","authenticated-orcid":false,"given":"Yoshinori","family":"Kadowaki","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/14787210.2023.2206565","article-title":"New insights into the treatment of acute otitis media","volume":"21","author":"Nedved","year":"2023","journal-title":"Expert Rev. 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