T-cell-biased immune responses generated by a mucosally targeted adenovirus-σ1 vaccine.

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.