Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA; Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
Cell Rep Med. 2024 Jan 16;5(1):101346. doi: 10.1016/j.xcrm.2023.101346. Epub 2023 Dec 20.
The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We develop a tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously (s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified β-lactoglobulin (BLG) is effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows superior safety and potential in treating existing allergies in combination with anti-CD20 co-therapy. This platform provides an antigen-specific immunomodulatory strategy to prevent and treat food allergies.
唯一经美国食品药品监督管理局批准的口服免疫疗法可预防花生过敏的意外暴露。然而，这种疗法常常引起不适或副作用，需要长期坚持。因此，迫切需要更好的预防和治疗方法。我们开发了一种诱导耐受的疫苗技术，该技术利用糖基化修饰抗原诱导抗原特异性无反应性。糖基化修饰抗原通过静脉内（i.v.）或皮下（s.c.）给药，分别流向肝脏或淋巴结，导致抗原呈递细胞优先内化，从而使免疫系统以无害的方式作出反应。在牛奶过敏的小鼠模型中，用糖基化修饰的β-乳球蛋白（BLG）治疗可有效预防过敏的发生。此外，与抗 CD20 联合治疗相结合，s.c.给予糖基化修饰的 BLG 显示出更好的安全性和治疗现有过敏的潜力。该平台提供了一种针对抗原的免疫调节策略，可预防和治疗食物过敏。
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