title: T-cell-biased immune responses generated by a mucosally targeted adenovirus-σ1 vaccine.
abstract: As 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 σ1 protein from reovirus to target junctional adhesion molecule 1 and sialic acid. Replication-defective Ad5 vectors were modified by replacement of the Ad fiber protein with σ1 (T3Dσ1) protein of reovirus T3D in previous work. Ad5 and Ad5-σ1 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. Ad5-σ1 was 40-fold less efficient at gene delivery in vivo, yet it was capable of inducing equal or greater cellular immune responses and systemic interferon-γ levels than Ad5 after intranasal administration. Despite weaker gross transduction, intranasal administration of Ad5-σ1 produced more green fluorescent protein-positive (GFP+) major histocompatibility complex class II (MHC II) cells in the draining lymph nodes, less GFP+/MHC II+ cells in the lungs, and mediated modestly better maturation of dendritic cells in vitro. These data suggest that targeting gene-based vaccination via the σ1 protein may enhance the T-cell immune response, perhaps by skewing immune responses to encoded antigens.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Weaver
authors.forename: G T
authors.initials: GT
authors.lastname: Mercier
authors.forename: S
authors.initials: S
authors.lastname: Gottschalk
authors.forename: M A
authors.initials: MA
authors.lastname: Barry
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000257:Adenoviridae Infections / Q000276:immunology* / Q000821:virology; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012087:Reoviridae / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus; D007371:Interferon-gamma