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Virology. 2015 Aug;482:60-6. doi: 10.1016/j.virol.2015.02.050. Epub 2015 Mar 30.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1.

Author information

1
Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA.
2
Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062, USA.
3
Nephrology Training Program, Mayo Clinic, Rochester, MN 55902, USA.
4
Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
5
Department of Physics, University of Houston, Houston, TX 77004, USA.
6
Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA; Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA. Electronic address: mab@mayo.edu.

Abstract

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination.

KEYWORDS:

Adenovirus; Immunization; Mucosal; Reovirus; Sigma 1

PMID:
25827529
PMCID:
PMC4461457
DOI:
10.1016/j.virol.2015.02.050
[Indexed for MEDLINE]
Free PMC Article

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