Academic Journal
Deimmunization of flagellin for repeated administration as a vaccine adjuvant
| العنوان: | Deimmunization of flagellin for repeated administration as a vaccine adjuvant |
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| المؤلفون: | Koemchhoy Khim, Yong Jun Bang, Sao Puth, Yoonjoo Choi, Youn Suhk Lee, Kwangjoon Jeong, Shee Eun Lee, Joon Haeng Rhee |
| المصدر: | npj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021) |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Flagellin, a protein-based Toll-like receptor agonist, is a versatile adjuvant applicable to wide spectrum of vaccines and immunotherapies. Given reiterated treatments of immunogenic biopharmaceuticals should lead to antibody responses precluding repeated administration, the development of flagellin not inducing specific antibodies would greatly expand the chances of clinical applications. Here we computationally identified immunogenic regions in Vibrio vulnificus flagellin B and deimmunized by simply removing a B cell epitope region. The recombinant deimmunized FlaB (dFlaB) maintains stable TLR5-stimulating activity. Multiple immunization of dFlaB does not induce FlaB-specific B cell responses in mice. Intranasally co-administered dFlaB with influenza vaccine enhanced strong Ag-specific immune responses in both systemic and mucosal compartments devoid of FlaB-specific Ab production. Notably, dFlaB showed better protective immune responses against lethal viral challenge compared with wild type FlaB. The deimmunizing B cell epitope deletion did not compromise stability and adjuvanticity, while suppressing unwanted antibody responses that may negatively affected vaccine antigen-directed immune responses in repeated vaccinations. We explain the underlying mechanism of deimmunization by employing molecular dynamics analysis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-0105 |
| Relation: | https://doaj.org/toc/2059-0105 |
| DOI: | 10.1038/s41541-021-00379-4 |
| URL الوصول: | https://doaj.org/article/a8f24b6ddcc2499695bfd6ace50b7b97 |
| رقم الانضمام: | edsdoj.8f24b6ddcc2499695bfd6ace50b7b97 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20590105 |
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| DOI: | 10.1038/s41541-021-00379-4 |