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Int. J. Mol. Sci. 2017, 18(10), 2137; doi:10.3390/ijms18102137

A Novel Multi-Epitope Vaccine Based on Urate Transporter 1 Alleviates Streptozotocin-Induced Diabetes by Producing Anti-URAT1 Antibody and an Immunomodulatory Effect in C57BL/6J Mice

School of Life Science & Technology, China Pharmaceutical University, Nanjing 210009, China
These authors contributed equally to this work.
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Received: 17 August 2017 / Revised: 28 September 2017 / Accepted: 30 September 2017 / Published: 16 October 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in streptozotocin-induced diabetes C57BL/6J mice successfully induced specific anti-URAT1 antibody, which inhibited URAT1 action and uric acid reabsorption, and increased pancreatic insulin level with a lower insulitis incidence. Vaccination with U-IA-2(5)-P2-1 (UIP-1) significantly reduced blood glucose and uric acid level, increased Th2 cytokines interleukin (IL)-10 and IL-4, and regulated immune reactions through a balanced Th1/Th2 ratio. These results demonstrate that the URAT1-based multi-epitope peptide vaccine may be a suitable therapeutic approach for diabetes and its complications. View Full-Text
Keywords: diabetes; hyperuricemia; urate transporter 1; uric acid; antibody diabetes; hyperuricemia; urate transporter 1; uric acid; antibody
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Ma, Y.; Cao, H.; Li, Z.; Fang, J.; Wei, X.; Cheng, P.; Jiao, R.; Liu, X.; Li, Y.; Xing, Y.; Tang, J.; Jin, L.; Li, T. A Novel Multi-Epitope Vaccine Based on Urate Transporter 1 Alleviates Streptozotocin-Induced Diabetes by Producing Anti-URAT1 Antibody and an Immunomodulatory Effect in C57BL/6J Mice. Int. J. Mol. Sci. 2017, 18, 2137.

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