A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes.

ABSTRACT: Type 1 diabetes (T1D) is caused by diabetogenic T cells that evaded tolerance mechanisms and react against multiple β-cell antigens. Antigen-specific therapy to reinstate tolerance (typically using a single β-cell antigen) has so far proved unsuccessful in T1D patients. Plasmid DNA (pDNA)-mediated expression of proinsulin has demonstrated transient protection in clinical trials, but long-lasting tolerance is yet to be achieved. We aimed to address whether pDNA delivery of multiple epitopes/mimotopes from several β-cell antigens efficiently presented to CD4⁺ and CD8⁺ T cells could also induce tolerance. This approach significantly delayed T1D development, while co-delivery of pDNA vectors expressing four full antigens protected more mice. Delivery of multiple epitopes

SUBMITTER: Postigo-Fernandez J 

PROVIDER: S-EPMC6389442 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature