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一种用于治疗自身免疫性疾病的无抗原前疫苗。

An antigen-less pro-vaccine for treating autoimmunity.

作者信息

Zheng Guoxing, Oo Thura Tun, Janjam Sri Sushma Santhi, Ellis Christian, Pallikonda Chakravarthy Sruthy, Palani Sunil, Anthon Wallace, Tsaras Gwendolyn, Williams Amanda, Feng Addysen, Chen Aoshuang

机构信息

Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL, United States.

Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.

出版信息

J Immunol. 2025 Jul 1;214(7):1477-1482. doi: 10.1093/jimmun/vkaf068.

Abstract

We have designed the first antigen-less pro-vaccine, named 8206, for treating autoimmune diseases. Composed of dexamethasone, rapamycin, and R848 at a mass ratio of 8:20:6, 8206 is a complete tolerogenic adjuvant that acts systemically to form an active vaccine in situ with endogenous pathogenic autoantigens. This active vaccine suppresses autoimmunity by expanding antigen-specific Treg cells in affected tissues. In a mouse model of atherosclerosis, 8206 successfully targeted all three analyzed pathogenic autoantigens (ApoB, HSP60, and HMGB1) and inhibited disease progression. These findings suggest that 8206 can potentially serve as a universal treatment vaccine for autoimmune diseases by eliminating the need for exogenous immunogens, with implications for broad applications in immunotherapy.

摘要

我们设计了首款用于治疗自身免疫性疾病的无抗原前疫苗,命名为8206。8206由地塞米松、雷帕霉素和R848按质量比8:20:6组成,是一种完全耐受性佐剂,可全身发挥作用,与内源性致病性自身抗原原位形成活性疫苗。这种活性疫苗通过在受影响组织中扩增抗原特异性调节性T细胞来抑制自身免疫。在动脉粥样硬化小鼠模型中,8206成功靶向了所有三种分析的致病性自身抗原(载脂蛋白B、热休克蛋白60和高迁移率族蛋白B1)并抑制了疾病进展。这些发现表明,8206有可能通过消除对外源免疫原的需求,作为一种通用的自身免疫性疾病治疗疫苗,对免疫治疗的广泛应用具有重要意义。

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