Abstract 11870: Development of a Novel Vaccine Against Dipeptidyl Peptidase-4 in Mice
Instruction and Hypothesis: The increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with a significant economic burden. We developed and assessed a novel dipeptidyl peptidase-4 (DPP4)-targeted immune therapy to increase glucagon like peptide 1 (GLP-1) hormone levels and improves insulin sensitivity for the prevention and treatment of T2DM.
Methods and Results: We selected 3 suitable regions in DPP4 as candidate targets for a vaccine and conjugated these peptides with keyhole limpet hemocyanin (KLH), which presents a variety of T cell epitopes to induce helper T cell responses. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased the DPP4 titer, inhibited the plasma DPP4 activity, and induced an increase in the plasma GLP-1 level. Moreover, this elevated titer was sustained for 3 months. We then assessed the efficacy of this vaccine in 2 animal models: high fat diet (HFD)-fed C57BL6/J mice and the diabetic kkAy and db/db mouse strains, which are commonly used as rodent models of insulin resistance and early onset T2DM, respectively. In mice fed a high fat diet (HFD), DPP4 vaccination resulted in improved postprandial glucose excursions, insulin sensitivity, and in the diabetic kkAy and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both the plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell mediated autoimmunity. Additionally, no significant immune mediated damage was detected in cells and tissues where DPP4 is expressed.
Conclusion: The DPP4 vaccine markedly improved insulin resistance and delayed the development of T2DM by increasing GLP-1 secretion without eliciting an autoimmune response. Thus, the DPP4 vaccine could provide an affordable and effective alternative for T2DM treatment.
Author Disclosures: Z. Pang: None.
- © 2014 by American Heart Association, Inc.