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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Yun, Jin-Seung Kim, Soo-Min Lee, Jin Sil Jeong, Su Hyun Oh, Hyeryeon Son, Panmo Kim, Sunghyun Lee, Young-Ran Shin, Eunkyung Ha, Sang-Jun Jung, Yong-Woo Kim, Dokeun Jeong, Hye-Sook Choi, Won Il |
| Abstract | Background Tuberculosis (TB) is a contagious disease and the second leading cause of death worldwide. The Bacille Calmette–Guérin (BCG) vaccine, the only licensed TB vaccine, has insufficient protective efficacy in adults, necessitating the development of new TB vaccines. Ag85B, a protein-subunit TB vaccine, is a promising candidate due to its high immunogenicity. However, its hydrophobicity presents challenges in manufacturing, expression, and purification, and Ag85B alone does not elicit sufficient immune stimulation. To overcome these limitations, this study aimed to design a temperature-responsive amine-terminated polylactic acid (PLA)-based nanosponge (aPNS) as both a nanoadjuvant and an efficient delivery carrier for Ag85B. Methods Ag85B was produced using an EZtag fusion tag vector, achieving high product yield and purity. It was then loaded into aPNS, a nanoparticle system with a PLA core and Pluronic shell, through a temperature-responsive process at 4 °C that preserved protein bioactivity. The stability and sustained-release profile of Ag85B@aPNS were evaluated. In vitro cytotoxicity and cellular uptake studies were conducted using macrophages. Protective efficacy and immunogenicity were assessed in M. tuberculosis-challenged mice and BCG-primed mice. Results The Ag85B protein was successfully produced and loaded into aPNS, which exhibited good colloidal stability and a sustained-release profile. Neither the synthesized Ag85B nor the aPNS showed significant cytotoxicity. aPNS enhanced the cellular uptake of antigens by macrophages. Compared to BCG, Ag85B@aPNS demonstrated superior protective efficacy against M. tuberculosis in mice and improved immunogenicity in BCG-primed mice. Conclusion Ag85B@aPNS is a viable candidate for TB vaccination, showing potential as both a standalone vaccine and a BCG-booster. Its ability to enhance immunogenicity and provide protection highlights its promise in addressing the limitations of current TB vaccines. |
| Related Links | https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-025-02105-2.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12964-025-02105-2 |
| Journal | Cell Communication and Signaling |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-04-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors PLA Nanosponge Nanoadjuvant New TB vaccine BCG-booster vaccine Tuberculosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Cell Biology Molecular Biology |
| Journal Impact Factor | 8.2/2023 |
| 5-Year Journal Impact Factor | 8/2023 |
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