T Cell-Biased Immune Responses Generated by a Mucosally-targeted Adenovirus-Sigma 1 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.

• Publication year

  2012

• Venue

  Mucosal Immunology

• Publication date

  2012-02-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/mi.2012.11PMID 22377931PMCID 3328625
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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