Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein
<b>Background/Objectives</b>: Acute otitis media is a common pediatric infection caused primarily by nontypeable <i>Haemophilus influenzae</i>. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway ha...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/3/313 |
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| Summary: | <b>Background/Objectives</b>: Acute otitis media is a common pediatric infection caused primarily by nontypeable <i>Haemophilus influenzae</i>. 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. <b>Methods</b>: BALB/c mice were intranasally immunized with nontypeable <i>H. influenzae</i> 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<sup>+</sup> T cells, T follicular helper (Tfh) cells, and B-cell differentiation were analyzed. <b>Results</b>: Anti-PD-L1 antibody treatment increased CD3<sup>+</sup>CD4<sup>+</sup>CD185<sup>+</sup> (CXCR5<sup>+</sup>) 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. <b>Conclusions</b>: 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. |
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| ISSN: | 2076-393X |