DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response

The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen...

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Main Authors: Trevor RF Smith, Katherine Schultheis, William B Kiosses, Dinah H Amante, Janess M Mendoza, John C Stone, Jay R McCoy, Niranjan Y Sardesai, Kate E Broderick
Format: Article
Language:English
Published: Elsevier 2014-01-01
Series:Molecular Therapy: Methods & Clinical Development
Online Access:http://www.sciencedirect.com/science/article/pii/S2329050116301231
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author Trevor RF Smith
Katherine Schultheis
William B Kiosses
Dinah H Amante
Janess M Mendoza
John C Stone
Jay R McCoy
Niranjan Y Sardesai
Kate E Broderick
author_facet Trevor RF Smith
Katherine Schultheis
William B Kiosses
Dinah H Amante
Janess M Mendoza
John C Stone
Jay R McCoy
Niranjan Y Sardesai
Kate E Broderick
author_sort Trevor RF Smith
collection DOAJ
description The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response.
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spelling doaj.art-cfbb15419d64485ab508a8b9d8400c6f2022-12-21T18:48:08ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012014-01-011C10.1038/mtm.2014.54DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune responseTrevor RF Smith0Katherine Schultheis1William B Kiosses2Dinah H Amante3Janess M Mendoza4John C Stone5Jay R McCoy6Niranjan Y Sardesai7Kate E Broderick8Inovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAThe Scripps Research Institute, Core Microscopy Facility, La Jolla, California, USAInovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAInovio Pharmaceuticals, San Diego, California, USAThe immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response.http://www.sciencedirect.com/science/article/pii/S2329050116301231
spellingShingle Trevor RF Smith
Katherine Schultheis
William B Kiosses
Dinah H Amante
Janess M Mendoza
John C Stone
Jay R McCoy
Niranjan Y Sardesai
Kate E Broderick
DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
Molecular Therapy: Methods & Clinical Development
title DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
title_full DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
title_fullStr DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
title_full_unstemmed DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
title_short DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response
title_sort dna vaccination strategy targets epidermal dendritic cells initiating their migration and induction of a host immune response
url http://www.sciencedirect.com/science/article/pii/S2329050116301231
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