title: Mucosal vaccination by adenoviruses displaying reovirus sigma 1.
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.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Weaver
authors.affiliation: Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062, USA.
authors.forename: Zenaido T
authors.initials: ZT
authors.lastname: Camacho
authors.affiliation: Nephrology Training Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hillestad
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Crosby
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Guenzel
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Hind J
authors.initials: HJ
authors.lastname: Fadel
authors.affiliation: Department of Physics, University of Houston, Houston, TX 77004, USA.
authors.forename: George T
authors.initials: GT
authors.lastname: Mercier
authors.affiliation: 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.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D061505:Cell Surface Display Techniques; D005260:Female; D005822:Genetic Vectors; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012087:Reoviridae / Q000235:genetics / Q000276:immunology*; D044967:Serum / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014621:Vagina / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C031728:sigma 1 protein, reovirus
keywords: Adenovirus; Immunization; Mucosal; Reovirus; Sigma 1
references.citation: J Virol. 2000 Jan;74(1):354-62
references.pmid: 10590124
references.citation: Mol Ther. 2003 Oct;8(4):688-700
references.pmid: 14529842
references.citation: J Biol Chem. 2003 Nov 28;278(48):48434-44
references.pmid: 12966102
references.citation: Trends Microbiol. 2004 Apr;12(4):162-9
references.pmid: 15051066
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6188-93
references.pmid: 15079060
references.citation: Nature. 1994 Oct 27;371(6500):802-6
references.pmid: 7523956
references.citation: J Clin Invest. 1997 Sep 1;100(5):1144-9
references.pmid: 9276731
references.citation: J Virol. 1999 Feb;73(2):907-19
references.pmid: 9882291
references.citation: Hum Gene Ther. 2004 Nov;15(11):1125-30
references.pmid: 15610612
references.citation: J Infect Dis. 2005 Apr 15;191(8):1221-4
references.pmid: 15776366
references.citation: Mol Ther. 2005 Sep;12(3):384-93
references.pmid: 15993650
references.citation: Methods Mol Med. 2007;130:169-83
references.pmid: 17401172
references.citation: J Virol. 2007 May;81(9):4654-63
references.pmid: 17329340
references.citation: Curr Gene Ther. 2007 Jun;7(3):189-204
references.pmid: 17584037
references.citation: PLoS Pathog. 2008 Dec;4(12):e1000235
references.pmid: 19079583
references.citation: Mol Ther. 2009 Aug;17(8):1333-9
references.pmid: 19513019
references.citation: Curr Gene Ther. 2011 Aug;11(4):241-58
references.pmid: 21453281
references.citation: Mucosal Immunol. 2012 May;5(3):311-9
references.pmid: 22377931
references.citation: Nat Rev Immunol. 2012 Aug;12(8):592-605
references.pmid: 22828912