College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam.
Adv Mater. 2023 Jan;35(1):e2202670. doi: 10.1002/adma.202202670. Epub 2022 Nov 22.
Herein, a tolerogenic nanovaccine is developed and tested on an animal model of multiple sclerosis. The nanovaccine is constructed to deliver the self-antigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and dexamethasone on an abatacept-modified polydopamine core nanoparticle (AbaLDPN-MOG). AbaLDPN-MOG can target dendritic cells and undergo endocytosis followed by trafficking to lysosomes. AbaLDPN-MOG blocks the interaction between CD80/CD86 and CD28 in antigen-presenting cells and T cells, leading to decreased interferon gamma secretion. The subcutaneous administration of AbaLDPN-MOG to mice yields significant biodistribution to lymph nodes and, in experimental-autoimmune encephalomyelitis (EAE) model mice, increases the integrity of the myelin basic sheath and minimizes the infiltration of immune cells. EAE mice are treated with AbaLDPN-MOG before or after injection of the autoantigen, MOG. Preimmunization of AbaLDPN-MOG before the injection of MOG completely blocks the development of clinical symptoms. Early treatment with AbaLDPN-MOG at three days after injection of MOG also completely blocks the development of symptoms. Notably, treatment of EAE symptom-developed mice with AbaLDPN-MOG significantly alleviates the symptoms, indicating that the nanovaccine has therapeutic effects. Although AbaLDPN is used for MOG peptide delivery in the EAE model, the concept of AbaLDPN can be widely applied for the prevention and alleviation of other autoimmune diseases.
本文开发了一种免疫耐受纳米疫苗，并在多发性硬化症的动物模型中进行了测试。该纳米疫苗构建用于递送自身抗原髓鞘少突胶质细胞糖蛋白 (MOG) 肽和地塞米松，在 abatacept 修饰的聚多巴胺核纳米颗粒 (AbaLDPN-MOG) 上。AbaLDPN-MOG 可以靶向树突状细胞并进行内吞作用，随后转运到溶酶体。AbaLDPN-MOG 阻断抗原呈递细胞和 T 细胞中 CD80/CD86 和 CD28 之间的相互作用，导致干扰素 γ 分泌减少。AbaLDPN-MOG 皮下给药于小鼠可显著分布于淋巴结，在实验性自身免疫性脑脊髓炎 (EAE) 模型小鼠中，增加髓鞘碱性蛋白的完整性并最小化免疫细胞的浸润。在注射自身抗原 MOG 之前或之后，用 AbaLDPN-MOG 治疗 EAE 小鼠。在注射 MOG 之前进行 AbaLDPN-MOG 的预免疫完全阻断了临床症状的发展。在注射 MOG 后三天早期用 AbaLDPN-MOG 治疗也完全阻断了症状的发展。值得注意的是，用 AbaLDPN-MOG 治疗出现 EAE 症状的小鼠显著缓解了症状，表明该纳米疫苗具有治疗效果。尽管 AbaLDPN 用于 EAE 模型中的 MOG 肽递送，但 AbaLDPN 的概念可以广泛应用于预防和缓解其他自身免疫性疾病。
