Oral Fc-Coupled Preproinsulin Achieves Systemic and Thymic Delivery Through the Neonatal Fc Receptor and Partially Delays Autoimmune Diabetes.

ABSTRACT: Tolerogenic vaccinations using beta-cell antigens are attractive for type 1 diabetes prevention, but clinical trials have been disappointing. This is probably due to the late timing of intervention, when multiple auto-antibodies are already present. We therefore devised a strategy to introduce the initiating antigen preproinsulin (PPI) during neonatal life, when autoimmunity is still silent and central tolerance mechanisms, which remain therapeutically unexploited, are more active. This strategy employs an oral administration of PPI-Fc, i.e. PPI fused with an IgG Fc to bind the intestinal neonatal Fc receptor (FcRn) that physiologically delivers maternal antibodies to the offspring during breastfeeding. Neonatal oral PPI-Fc vaccination did not prevent diabetes development in PPI T-cell rec

SUBMITTER: Corcos N 

PROVIDER: S-EPMC8382691 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature