Diabetes tolerogenic vaccines targeting antigen-specific inflammation

Geng, Shuang; Zhang, Huiyuan; Zhou, Xian; He, Yue; Zhang, Xiaoqian; Xie, Xiaoping; Li, Chaofan; He, Zhonghuai; Yu, Qingling; Zhong, Yiwei; Lowrie, Douglas B.; Zheng, Guoxing; Wang, Bin

doi:10.1080/21645515.2014.1004024

Cited by 7 publications

(5 citation statements)

References 75 publications

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“…The use of Tregs as a method to treat inflammation and autoimmune diseases has been proposed and well-received by scientists (30). Many clinical trials have proved that the use of vaccines to treat autoimmune diseases cannot effectively induce the production of antigen-specific Treg cells, thus inhibiting the role of pathological T cells.…”

Section: Discussionmentioning

confidence: 99%

“…Treg is a subset of CD4 + T cells which are characterized by the expression of transcription factor Foxp3 and helps to keep inflammation under control and lower the autoimmune disease risk in healthy individuals (30). They have been proved to maintain their regulatory functions for a long-term even in the absence of antigens that induced their generation and are stable and transferable (31), thereby permitting the expected induction of these cells to suppress unwanted immunity (13).…”

Section: Gad65 Phage Vaccine + Kyn Increases Cd4 + Cd25 + Treg Cells In the Nod Mouse Modelmentioning

confidence: 99%

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The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine

Sun

Shi

et al. 2021

Front. Immunol.

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Inducing antigen-specific tolerance is a promising treatment for preventing or reversing Type 1 diabetes (T1D). In contrast to a vaccine that induces immune responses against pathogens, a tolerogenic vaccine can suppress immunity against antigens causing diseases by administrating a mixture of self-antigens with an adjuvant that decreases the strength of antigen-specific response. Kynurenine (Kyn) is an endogenous substance that can inhibit the natural killer cell and T cell proliferation and promote the differentiation of naïve T cells into regulatory T cells (Tregs). In this study, we evaluated the efficacy of Kyn as a novel suppressive adjuvant. Kyn was co-immunized with GAD65 phage vaccine to induce Treg cells and tolerogenic responses for the prevention of T1D in NOD mouse model. Mice were subcutaneously immunized two times with 1011 Pfu (100μL,1012 Pfu/ml) GAD65 phage vaccine doses mixed with 200 μg of Kyn. Serum antibodies and cytokines were detected by ELISA and electrochemiluminescence, respectively. Flow cytometry assay was used to analyze DC and Treg. MTS was used for the analysis of spleen lymphocyte proliferation. RNA sequencing was used to investigate mRNA and miRNA expression profiles in spleen lymphocytes. Compared to GAD65 phage vaccine alone, co-immunization of Kyn and GAD65 phage vaccine resulted in the prevention of hyperglycemia in 60% of mice for at least one month. Further, Kyn enhances GAD65-specific Th2-mediated immune responses; regulates the Th1/Th2 imbalance and increases the secretion of Th2 cytokines and the number of CD4+CD25+Foxp3+T cells; suppresses DC maturation and GAD65-specific T lymphocyte proliferation. Moreover, we integrated Kyn related miRNA and mRNA expression profiles obtained from the spleen lymphocyte RNA-sequencing which was stimulated by Kyn in vitro. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant which regulated the immune response. These findings suggest that Kyn can serve as an effective suppressive adjuvant candidate for Type 1 diabetes vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Gad65 Phage Vaccine + Kyn Increases Cd4 + Cd25 + Treg Cells In the Nod Mouse Modelmentioning

confidence: 99%

The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine

Sun

Shi

et al. 2021

Front. Immunol.

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“…Recently, the proof-of-concept for using RNA as tolerogenic vaccine was provided. In contrast to a vaccine augmenting immune responses against a pathogen, a tolerogenic vaccine is aimed at inducing tolerogenic responses to suppress or impair immunity against antigens, which in most cases are auto-antigens or allergens (Geng et al 2015) . Such vaccines may help in managing autoimmune diseases.…”

Section: Applications Of Rna Therapeuticsmentioning

confidence: 99%

Hospital-based RNA Therapeutics

Damase¹,

Sukhovershin²,

Zhang³

et al. 2022

Preprint

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Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

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“…Dendritic cells, a major type of innate immune cells involved in the regulation of T cell activation, inflammation, as well as tumor microenvironment [11], is considered to be a potent mediator bridging the innate and adaptive immune systems [12,13]. It could uptake and present the tumour-specific antigens to activate CD4 + or CD8 + T cell response [14].…”

Section: Regulation Of Innate Immune Response By Dubsmentioning

confidence: 99%

Deubiquitinase as Potential Targets for Cancer Immunotherapy

2019

Journal of Cellular Immunology

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Diabetes tolerogenic vaccines targeting antigen-specific inflammation

Cited by 7 publications

References 75 publications

The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine

The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine

Hospital-based RNA Therapeutics

Deubiquitinase as Potential Targets for Cancer Immunotherapy

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