title: Antigen-based vaccination and prevention of type 1 diabetes.
abstract: Insulin-dependent or type 1 diabetes (T1D) is a paradigm for prevention of autoimmune disease: Pancreatic β-cell autoantigens are defined, at-risk individuals can be identified before the onset of symptoms, and autoimmune diabetes is preventable in rodent models. Intervention in asymptomatic individuals before or after the onset of subclinical islet autoimmunity places a premium on safety, a requirement met only by lifestyle-dietary approaches or autoantigen-based vaccination to induce protective immune tolerance. Insulin is the key driver of autoimmune β-cell destruction in the nonobese diabetic (NOD) mouse model of T1D and is an early autoimmune target in children at risk for T1D. In the NOD mouse, mucosal administration of insulin induces regulatory T cells that protect against diabetes. The promise of autoantigen-specific vaccination in humans has yet to be realized, but recent trials of oral and nasal insulin vaccination in at-risk humans provide grounds for cautious optimism.
authors.affiliation: Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052, Victoria, Australia, harrison@wehi.edu.au.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
authors.forename: John M
authors.initials: JM
authors.lastname: Wentworth
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Esther
authors.initials: E
authors.lastname: Bandala-Sanchez
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Böhmer
authors.forename: Alana M
authors.initials: AM
authors.lastname: Neale
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Stone
authors.forename: Gaetano
authors.initials: G
authors.lastname: Naselli
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Bosco
authors.forename: Priscilla
authors.initials: P
authors.lastname: Auyeung
authors.forename: Maryam
authors.initials: M
authors.lastname: Rashidi
authors.forename: Petra
authors.initials: P
authors.lastname: Augstein
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D014611:Vaccination
chemical_list: D001324:Autoantigens; D007328:Insulin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2