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T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine
INTRODUCTION: Since, most pathogens enter through the mucosa it is important to develop vaccines that induce mucosal immunity. To this end, we generated a novel adenovirus (Ad) vaccine that displays the sigma1 protein from reovirus to target junctional adhesion molecule 1 (JAM1) and sialic acid. MAT...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328625/ https://www.ncbi.nlm.nih.gov/pubmed/22377931 http://dx.doi.org/10.1038/mi.2012.11 |
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author | Weaver, Eric A. Mercier, George T. Gottschalk, Stephen Barry, Michael A. |
author_facet | Weaver, Eric A. Mercier, George T. Gottschalk, Stephen Barry, Michael A. |
author_sort | Weaver, Eric A. |
collection | PubMed |
description | INTRODUCTION: Since, most pathogens enter through the mucosa it is important to develop vaccines that induce mucosal immunity. To this end, we generated a novel adenovirus (Ad) vaccine that displays the sigma1 protein from reovirus to target junctional adhesion molecule 1 (JAM1) and sialic acid. MATERIALS/METHODS: Replication-defective Ad5 vectors were modified by replacement of the Ad fiber protein with Sigma 1 (T3Dσ1) protein of reovirus T3D in previous work. Ad5 and Ad5-Sigma1 were compared in mouse models for gene delivery and vaccination to monitor cytokine, antibody, and T cell responses. The viruses were also tested for the ability to transduce and mature dendritic cells. RESULTS/CONCLUSIONS: Ad5-Sigma1 was 40-fold less efficient at gene delivery in vivo, yet was capable of inducing equal or greater cellular immune responses and systemic IFN-γ levels than Ad5 after intranasal administration. Despite weaker gross transduction, intranasal administration of Ad5-Sigma1 produced more GFP-positive MHCII cells in the draining lymph nodes, less GFP+/MHCII+ cells in the lungs and mediated modestly better maturation of dendritic cells in vitro. These data suggest that targeting gene-based vaccination via the Sigma1 protein may enhance the T cell immune response perhaps by skewing immune responses to encoded antigens. |
format | Online Article Text |
id | pubmed-3328625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33286252012-11-01 T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine Weaver, Eric A. Mercier, George T. Gottschalk, Stephen Barry, Michael A. Mucosal Immunol Article INTRODUCTION: Since, most pathogens enter through the mucosa it is important to develop vaccines that induce mucosal immunity. To this end, we generated a novel adenovirus (Ad) vaccine that displays the sigma1 protein from reovirus to target junctional adhesion molecule 1 (JAM1) and sialic acid. MATERIALS/METHODS: Replication-defective Ad5 vectors were modified by replacement of the Ad fiber protein with Sigma 1 (T3Dσ1) protein of reovirus T3D in previous work. Ad5 and Ad5-Sigma1 were compared in mouse models for gene delivery and vaccination to monitor cytokine, antibody, and T cell responses. The viruses were also tested for the ability to transduce and mature dendritic cells. RESULTS/CONCLUSIONS: Ad5-Sigma1 was 40-fold less efficient at gene delivery in vivo, yet was capable of inducing equal or greater cellular immune responses and systemic IFN-γ levels than Ad5 after intranasal administration. Despite weaker gross transduction, intranasal administration of Ad5-Sigma1 produced more GFP-positive MHCII cells in the draining lymph nodes, less GFP+/MHCII+ cells in the lungs and mediated modestly better maturation of dendritic cells in vitro. These data suggest that targeting gene-based vaccination via the Sigma1 protein may enhance the T cell immune response perhaps by skewing immune responses to encoded antigens. 2012-02-29 2012-05 /pmc/articles/PMC3328625/ /pubmed/22377931 http://dx.doi.org/10.1038/mi.2012.11 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Weaver, Eric A. Mercier, George T. Gottschalk, Stephen Barry, Michael A. T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title | T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title_full | T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title_fullStr | T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title_full_unstemmed | T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title_short | T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 Vaccine |
title_sort | t cell-biased immune responses generated by a mucosally-targeted adenovirus-sigma 1 vaccine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328625/ https://www.ncbi.nlm.nih.gov/pubmed/22377931 http://dx.doi.org/10.1038/mi.2012.11 |
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