Deimmunization of flagellin for repeated administration as a vaccine adjuvant
Autor: | Joon Haeng Rhee, Yoonjoo Choi, Youn Suhk Lee, Shee Eun Lee, Koemchhoy Khim, Sao Puth, Yong Jun Bang, Kwangjoon Jeong |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Pharmacology
biology Influenza vaccine medicine.medical_treatment Immunology Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC581-607 Translational research Epitope Article Vaccination Infectious Diseases medicine.anatomical_structure Immune system medicine biology.protein Pharmacology (medical) Adjuvants Immunologic diseases. Allergy Adjuvant Deimmunization Flagellin B cell RC254-282 |
Zdroj: | NPJ Vaccines npj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021) |
ISSN: | 2059-0105 |
Popis: | 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. |
Databáze: | OpenAIRE |
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