Oral delivery of the intracellular domain of the insulinoma-associated protein 2 (IA-2ic) by bacterium-like particles (BLPs) prevents type 1 diabetes mellitus in NOD mice.

Abstract	Antigen-specific immune tolerance, which possesses great potential in preventing or curing type 1 diabetes mellitus (T1DM), can be induced by oral vaccination with T1DM-related autoantigens. However, direct administration of autoantigens via oral route exhibits a low tolerance-inducing effect as a result of the digestion of protein antigens in the gastrointestinal tract (GIT) and therefore, a large dosage of autoantigens may be needed. In this study, bacterium-like particles (BLPs) made from food-grade lactic acid bacteria were used to deliver the intracellular domain of the insulinoma-associated protein 2 (IA-2ic). For this purpose, BLPs-IA-2ic vaccine in which IA-2ic bound to the surface of BLPs was constructed. BLPs enhanced the stability of the delivered IA-2ic based on the stability analysis in vitro. Oral administration of BLPs-IA-2ic significantly reduced T1DM incidence in NOD mice. The mice fed BLPs-IA-2ic exhibited a significant reduction in insulitis and preserved the ability to secrete insulin. Immunologic analysis showed that oral vaccination with BLPs-IA-2ic induced antigen-specific T cell tolerance. The results revealed that the successful induction of immune tolerance was dependent on the immune deviation (in favor of T helper 2 responses) and CD4+CD25+FoxP3+ regulatory T cells. Hence, oral vaccination with BLPs-IA-2ic shows potential for application in preventing T1DM.
Authors	Ruifeng Mao, Menglan Yang, Rui Yang, Yingying Chen, Enjie Diao, Tong Zhang, Dengchao Li, Xin Chang, Zhenjing Chi, Yefu Wang
Journal	Drug delivery (Drug Deliv) Vol. 29 Issue 1 Pg. 925-936 (Dec 2022) ISSN: 1521-0464 [Electronic] England
PMID	35311607 (Publication Type: Journal Article)
Chemical References	Autoantigens Insulin Receptor-Like Protein Tyrosine Phosphatases, Class 8
Topics	Animals Autoantigens (administration & dosage) Diabetes Mellitus, Type 1 (prevention & control) Insulin Mice Mice, Inbred NOD Receptor-Like Protein Tyrosine Phosphatases, Class 8 (administration & dosage) T-Lymphocytes, Regulatory

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