Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice
Ruifeng Mao,
Jin Wang,
Ying Xu,
Yuqi Wang,
Mengmeng Wu,
Lixia Mao,
Yingying Chen,
Dengchao Li,
Tong Zhang,
Enjie Diao,
Zhenjing Chi,
Yefu Wang,
Xin Chang
Affiliations
Ruifeng Mao
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Yuqi Wang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Mengmeng Wu
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Lixia Mao
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Yingying Chen
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Dengchao Li
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Tong Zhang
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Enjie Diao
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, China
Zhenjing Chi
Huai’an First People’s Hospital, Nanjing Medical University, Huai’an223300, China
Yefu Wang
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan430072, China
AbstractInduction of oral tolerance by vaccination with type 1 diabetes mellitus (T1DM)-associated autoantigens exhibits great potential in preventing and treating this autoimmune disease. However, antigen degradation in the gastrointestinal tract (GIT) limits the delivery efficiency of oral antigens. Previously, bacterium-like particles (BLPs) have been used to deliver a single-chain insulin (SCI-59) analog (BLPs-SCI-59) or the intracellular domain of insulinoma-associated protein 2 (IA-2ic) (BLPs-IA-2ic). Both monovalent BLPs vaccines can suppress T1DM in NOD mice by stimulating the corresponding antigen-specific oral tolerance, respectively. Here, we constructed two bivalent BLPs vaccines which simultaneously deliver SCI-59 and IA-2ic (Bivalent vaccine-mix or Bivalent vaccine-SA), and evaluated whether there is an additive beneficial effect on tolerance induction and suppression of T1DM by treatment with BLPs-delivered bi-autoantigens. Compared to the monovalent BLPs vaccines, oral administration of the Bivalent vaccine-mix could significantly reduce morbidity and mortality in T1DM. Treatment with the bivalent BLPs vaccines (especially Bivalent vaccine-mix) endowed the mice with a stronger ability to regulate blood glucose and protect the integrity and function of pancreatic islets than the monovalent BLPs vaccines treatment. This additive effect of BLPs-delivered bi-autoantigens on T1DM prevention may be related to that SCI-59- and IA-2-specific Th2-like immune responses could be induced, which was more beneficial for the correction of Th1/Th2 imbalance. In addition, more CD4+CD25+Foxp3+ regulatory T cells (Tregs) were induced by treatment with the bivalent BLPs vaccines than did the monovalent BLPs vaccines. Therefore, multiple autoantigens delivered by BLPs maybe a promising strategy to prevent T1DM by efficiently inducing antigen-specific immune tolerance.
