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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 |
Sumario: | 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. |
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