Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice
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 antigen...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2023.2173339 |
| _version_ | 1797260953178341376 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ruifeng Mao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T23:31:57Z |
| format | Article |
| id | doaj.art-9809eb1192604a52b60c2633ce824dce |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:33:30Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-9809eb1192604a52b60c2633ce824dce2024-03-15T14:22:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130110.1080/10717544.2023.2173339Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD miceRuifeng Mao0Jin Wang1Ying Xu2Yuqi Wang3Mengmeng Wu4Lixia Mao5Yingying Chen6Dengchao Li7Tong Zhang8Enjie Diao9Zhenjing Chi10Yefu Wang11Xin Chang12Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaNanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing211200, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaJiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, School of Life Sciences, Huaiyin Normal University, Huai’an223300, ChinaHuai’an First People’s Hospital, Nanjing Medical University, Huai’an223300, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan430072, ChinaNanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing211200, ChinaAbstractInduction 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.https://www.tandfonline.com/doi/10.1080/10717544.2023.2173339Type 1 diabetes mellitusimmune toleranceautoantigenbacterium-like particlesoral vaccination |
| spellingShingle | 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 Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice Drug Delivery Type 1 diabetes mellitus immune tolerance autoantigen bacterium-like particles oral vaccination |
| title | Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice |
| title_full | Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice |
| title_fullStr | Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice |
| title_full_unstemmed | Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice |
| title_short | Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice |
| title_sort | oral delivery of bi autoantigens by bacterium like particles blps against autoimmune diabetes in nod mice |
| topic | Type 1 diabetes mellitus immune tolerance autoantigen bacterium-like particles oral vaccination |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2023.2173339 |
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