Khim Koemchhoy, Puth Sao, Radhakrishnan Kamalakannan, Nguyen Tien Duc, Lee Youn Suhk, Jung Che-Hun, Lee Shee Eun, Rhee Joon Haeng
Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun, Jeonnam, Republic of Korea.
Combinatorial Tumor Immunotherapy MRC, Chonnam National University Medical School, Hwasun-gun, Jeonnam, Republic of Korea.
NPJ Vaccines. 2023 Sep 26;8(1):139. doi: 10.1038/s41541-023-00738-3.
Flagellin, the TLR5 agonist, shows potent adjuvant activities in diverse vaccines and immunotherapies. Vibrio vulnificus flagellin B expressed in eukaryotic cells (eFlaB) could not stimulate TLR5 signaling. Enzymatic deglycosylation restored eFlaB's TLR5 stimulating functionality, suggesting that glycosylation interferes with eFlaB binding to TLR5. Site-directed mutagenesis of N-glycosylation residues restored TLR5 stimulation and adjuvanticity. Collectively, deglycosylated eFlaB may provide a built-in adjuvant platform for eukaryotic-expressed antigens and nucleic acid vaccines.
鞭毛蛋白作为Toll样受体5（TLR5）激动剂，在多种疫苗和免疫疗法中显示出强大的佐剂活性。在真核细胞中表达的创伤弧菌鞭毛蛋白B（eFlaB）不能刺激TLR5信号传导。酶促去糖基化恢复了eFlaB刺激TLR5的功能，这表明糖基化会干扰eFlaB与TLR5的结合。对N-糖基化残基进行定点诱变可恢复TLR5刺激和佐剂活性。总的来说，去糖基化的eFlaB可能为真核表达抗原和核酸疫苗提供一个内置的佐剂平台。
