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

Eric A Weaver, G. T. Mercier, S. Gottschalk, M. A. Barry

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalMucosal Immunology
Volume5
Issue number3
DOIs
StatePublished - May 1 2012

Fingerprint

Adenovirus Vaccines
Intranasal Administration
Green Fluorescent Proteins
Major Histocompatibility Complex
T-Lymphocytes
Dendritic Cells
Junctional Adhesion Molecules
Vaccination
Mammalian Orthoreovirus
Mucosal Immunity
Proteins
Gene Targeting
N-Acetylneuraminic Acid
Cellular Immunity
Interferons
Genes
Mucous Membrane
Vaccines
Lymph Nodes
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

T-cell-biased immune responses generated by a mucosally targeted adenovirus-σ1 vaccine. / Weaver, Eric A; Mercier, G. T.; Gottschalk, S.; Barry, M. A.

In: Mucosal Immunology, Vol. 5, No. 3, 01.05.2012, p. 311-319.

Research output: Contribution to journalArticle

Weaver, Eric A ; Mercier, G. T. ; Gottschalk, S. ; Barry, M. A. / T-cell-biased immune responses generated by a mucosally targeted adenovirus-σ1 vaccine. In: Mucosal Immunology. 2012 ; Vol. 5, No. 3. pp. 311-319.
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