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Title: Mucosal vaccination by adenoviruses displaying reovirus sigma 1

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. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.
Authors:
 [1] ;  [2] ;  [3] ; ; ; ;  [4] ;  [5] ;  [1] ;  [6]
  1. Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States)
  2. Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States)
  3. Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States)
  4. Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States)
  5. Department of Physics, University of Houston, Houston, TX 77004 (United States)
  6. (United States)
Publication Date:
OSTI Identifier:
22470177
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 482; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOVIRUS; ANTIBODIES; CHIMERAS; COMPARATIVE EVALUATIONS; DELIVERY; FIBERS; GENES; IN VITRO; LENGTH; MICE; PROTEINS; SIALIC ACID; VACCINES