Deimmunization of flagellin for repeated administration as a vaccine adjuvant

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Koemchhoy Khim, Yong Jun Bang, Sao Puth, Yoonjoo Choi, Youn Suhk Lee, Kwangjoon Jeong, Shee Eun Lee, Joon Haeng Rhee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a8f24b6ddcc2499695bfd6ace50b7b97
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a8f24b6ddcc2499695bfd6ace50b7b97
record_format	dspace
spelling	oai:doaj.org-article:a8f24b6ddcc2499695bfd6ace50b7b972021-12-02T17:25:42ZDeimmunization of flagellin for repeated administration as a vaccine adjuvant10.1038/s41541-021-00379-42059-0105https://doaj.org/article/a8f24b6ddcc2499695bfd6ace50b7b972021-09-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00379-4https://doaj.org/toc/2059-0105Abstract 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.Koemchhoy KhimYong Jun BangSao PuthYoonjoo ChoiYoun Suhk LeeKwangjoon JeongShee Eun LeeJoon Haeng RheeNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Koemchhoy Khim Yong Jun Bang Sao Puth Yoonjoo Choi Youn Suhk Lee Kwangjoon Jeong Shee Eun Lee Joon Haeng Rhee Deimmunization of flagellin for repeated administration as a vaccine adjuvant
description	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.
format	article
author	Koemchhoy Khim Yong Jun Bang Sao Puth Yoonjoo Choi Youn Suhk Lee Kwangjoon Jeong Shee Eun Lee Joon Haeng Rhee
author_facet	Koemchhoy Khim Yong Jun Bang Sao Puth Yoonjoo Choi Youn Suhk Lee Kwangjoon Jeong Shee Eun Lee Joon Haeng Rhee
author_sort	Koemchhoy Khim
title	Deimmunization of flagellin for repeated administration as a vaccine adjuvant
title_short	Deimmunization of flagellin for repeated administration as a vaccine adjuvant
title_full	Deimmunization of flagellin for repeated administration as a vaccine adjuvant
title_fullStr	Deimmunization of flagellin for repeated administration as a vaccine adjuvant
title_full_unstemmed	Deimmunization of flagellin for repeated administration as a vaccine adjuvant
title_sort	deimmunization of flagellin for repeated administration as a vaccine adjuvant
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a8f24b6ddcc2499695bfd6ace50b7b97
work_keys_str_mv	AT koemchhoykhim deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT yongjunbang deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT saoputh deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT yoonjoochoi deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT younsuhklee deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT kwangjoonjeong deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT sheeeunlee deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant AT joonhaengrhee deimmunizationofflagellinforrepeatedadministrationasavaccineadjuvant
_version_	1718380928016842752

Deimmunization of flagellin for repeated administration as a vaccine adjuvant

Ejemplares similares