Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy

被引:4
|
作者
Cao, Shijie [1 ,2 ]
Maulloo, Chitavi D. [1 ]
Raczy, Michal M. [1 ]
Sabados, Matthew [3 ]
Slezak, Anna J. [1 ]
Nguyen, Mindy [1 ,4 ]
Solanki, Ani [1 ,4 ]
Wallace, Rachel P. [1 ]
Shim, Ha-Na [1 ]
Wilson, D. Scott [1 ,5 ]
Hubbell, Jeffrey A. [1 ,6 ,7 ]
机构
[1] Univ Chicago, Pritzker Sch Mol Engn, Chicago, IL 60637 USA
[2] Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA
[3] Univ Chicago, Biol Sci Div, Chicago, IL 60637 USA
[4] Univ Chicago, Anim Resource Ctr, Chicago, IL 60637 USA
[5] Johns Hopkins Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA
[6] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA
[7] Univ Chicago, Comm Canc Biol, Chicago, IL 60637 USA
关键词
MANNOSE RECEPTOR; PEANUT ALLERGY; IMMUNOTHERAPY; IGE; HOMEOSTASIS; MICROBIOME; MECHANISMS; CELLS;
D O I
10.1016/j.xcrm.2023.101346
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 toleranceinducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen -specific nonresponsiveness. 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 antigenpresenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified b-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.
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页数:18
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