Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-8-22
pubmed:abstractText
Oral administration of autoantigens and allergens can delay or suppress clinical disease in experimental autoimmune and allergic disorders. However, repeated feeding of large amounts of the tolerogens is required over long periods and is only partially effective in animals systemically sensitized to the ingested antigen. Enhanced suppression of type 1 autoimmune diabetes insulitis and hyperglycemia was demonstrated in both naive and immune animals following oral inoculation with plant-based antigens coupled to the cholera toxin B subunit (CTB). Thus, plant-synthesized antigens linked to the CTB adjuvant, can enhance suppression of inflammatory TH1 lymphocyte-mediated autoreactivity in both naive and immune animals. To stimulate adjuvant-autoantigen fusion protein biosynthesis in the gut mucosae, the authors evaluated oral inoculation of juvenile non-obese diabetic (NOD) mice with recombinant vaccinia virus (rVV) expressing fusion genes encoding CTB linked to the pancreatic islet autoantigens proinsulin (INS) and a 55-kDa C-terminal peptide from glutamate decarboxylase (GAD55). Hyperglycemia in both rVV-CTB:: INS and rVV-CTB:: GAD inoculated mice was substantially reduced in comparison with the uninoculated mouse control. Oral inoculation with rVV carrying the CTB::INS fusion gene generated a significant reduction in insulitis. An increase in IgG1 in comparison with IgG2c antibody isotype titers in rVV-CTB::INS infected mice suggested possible activation of autoantigen specific Th2 lymphocytes. The experimental results demonstrate feasibility of using vaccinia virus oral delivery of adjuvanted autoantigens to the mucosae of prediabetic mice for suppression and therapy of type 1 autoimmune diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1524-9557
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
438-48
pubmed:dateRevised
2008-3-18
pubmed:meshHeading
pubmed-meshheading:16113600-Administration, Oral, pubmed-meshheading:16113600-Adoptive Transfer, pubmed-meshheading:16113600-Animals, pubmed-meshheading:16113600-Autoantigens, pubmed-meshheading:16113600-COS Cells, pubmed-meshheading:16113600-Caco-2 Cells, pubmed-meshheading:16113600-Cell Line, Tumor, pubmed-meshheading:16113600-Cercopithecus aethiops, pubmed-meshheading:16113600-Diabetes Mellitus, Type 1, pubmed-meshheading:16113600-Disease Models, Animal, pubmed-meshheading:16113600-Female, pubmed-meshheading:16113600-Glutamate Decarboxylase, pubmed-meshheading:16113600-Humans, pubmed-meshheading:16113600-Immune Tolerance, pubmed-meshheading:16113600-Immunoblotting, pubmed-meshheading:16113600-Immunoglobulin G, pubmed-meshheading:16113600-Immunohistochemistry, pubmed-meshheading:16113600-Intestines, pubmed-meshheading:16113600-Islets of Langerhans, pubmed-meshheading:16113600-Isoenzymes, pubmed-meshheading:16113600-Mice, pubmed-meshheading:16113600-Mice, Inbred NOD, pubmed-meshheading:16113600-Peptides, pubmed-meshheading:16113600-Plasmids, pubmed-meshheading:16113600-Proinsulin, pubmed-meshheading:16113600-Recombinant Fusion Proteins, pubmed-meshheading:16113600-Th2 Cells, pubmed-meshheading:16113600-Time Factors, pubmed-meshheading:16113600-Vaccinia virus
pubmed:articleTitle
Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens.
pubmed:affiliation
Center for Molecular Biology and Gene Therapy, Department of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural