Therapeutic vaccine against DPP4 improves glucose metabolism in mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 13; pp. E1256 - E1263
• Main Authors: Pang, Zhengda, Nakagami, Hironori, Osako, Mariana K, Koriyama, Hiroshi, Nakagami, Futoshi, Tomioka, Hideki, Shimamura, Munehisa, Kurinami, Hitomi, Takami, Yoichi, Morishita, Ryuichi, Rakugi, Hiromi
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.04.2014; National Acad Sciences
• Series: PNAS Plus
• Subjects: Amino Acid Sequence; Animals; Antigens - chemistry; Antigens - immunology; Biological Sciences; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - prevention & control; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - prevention & control; Diet, High-Fat; Dipeptidyl Peptidase 4 - immunology; Disease Models, Animal; Glucose - metabolism; Immunity (Disease); Immunization; Immunotherapy; Insulin Resistance - immunology; Lymphocyte Activation - immunology; Male; Mice; Mice, Inbred C57BL; Peptides; Peptides - chemistry; Peptides - immunology; PNAS Plus; T-Lymphocytes - immunology; Treatment Outcome; Vaccination; Vaccines; Vaccines - immunology; Vaccines - therapeutic use
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1322009111

The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK- A ʸ and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both 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. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes.