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9-Phenanthrol enhances the generation of an CD8 + T cell response following transcutaneous immunization with imiquimod in mice.
- Source :
-
Journal of dermatological science [J Dermatol Sci] 2017 Sep; Vol. 87 (3), pp. 260-267. Date of Electronic Publication: 2017 Aug 12. - Publication Year :
- 2017
-
Abstract
- Background: Transcutaneous immunization (TCI) is a non-invasive vaccination strategy targeting the skin-associated lymphoid tissue. Topical application of the TLR7 agonist imiquimod as adjuvant in combination with peptide antigens activates the innate immune system and mounts cytotoxic T lymphocyte (CTL) responses.<br />Objective: Based on the commercial 5% imiquimod-containing drug Aldara we aimed to develop an improved formulation with superior vaccination efficiencies. The primary target was the enhancement of mast cell activation as important key for the function of the innate immune system.<br />Methods: We investigated the effects of 9-phenanthrol (9-phe) on the activation of mast cells in vitro and in vivo. For TCI, we applied 0.2% 9-phe in Aldara or Aldara alone as adjuvants in combination with the MHC class I - restricted peptide SIINFEKL. To monitor vaccination, mast cell degranulation, migration of DC and frequencies of epitope-specific CTL was assessed. In a transgenic tumor model, the efficiencies of prophylactic immunization against a tumor antigen were also monitored.<br />Results: 9-phe induced degranulation of mast cells in vitro and upon topical application in vivo. A mixture of 0.2% 9-phe in Aldara showed superior results regarding the migration of DC and the expansion of antigen-specific CTL. Consequently, prophylactic immunization with 0.2% 9-phe in Aldara caused enhanced protection against tumor inoculation.<br />Conclusion: Our data demonstrate that a simple modification of an adjuvant formulation can yield superior results in experimental vaccination protocols by boosting critical steps leading to the generation of an efficient CTL response.<br /> (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adjuvants, Immunologic therapeutic use
Administration, Cutaneous
Aminoquinolines pharmacology
Aminoquinolines therapeutic use
Animals
Calcium metabolism
Cell Movement
Dendritic Cells drug effects
Dendritic Cells immunology
Humans
Imiquimod
Immunity, Innate drug effects
Mast Cells immunology
Mast Cells metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenanthrenes pharmacology
Phenanthrenes therapeutic use
Protein Kinase Inhibitors therapeutic use
Skin cytology
Skin drug effects
Skin immunology
T-Lymphocytes, Cytotoxic immunology
Vaccination methods
Xenograft Model Antitumor Assays
Adjuvants, Immunologic pharmacokinetics
Cell Degranulation drug effects
Mast Cells drug effects
Melanoma prevention & control
Protein Kinase Inhibitors pharmacology
Skin Neoplasms prevention & control
T-Lymphocytes, Cytotoxic drug effects
TRPM Cation Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-569X
- Volume :
- 87
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of dermatological science
- Publication Type :
- Academic Journal
- Accession number :
- 28823644
- Full Text :
- https://doi.org/10.1016/j.jdermsci.2017.07.018