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PG-tb1 单价糖缀合物的合成与免疫原性。

Synthesis and immunogenicity of PG-tb1 monovalent glycoconjugate.

机构信息

China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.

Affiliated Hospital of Logistic University of Chinese People's Armed Police Force (PAPF), Tianjin 300162, China.

出版信息

Eur J Med Chem. 2017 Jul 7;134:140-146. doi: 10.1016/j.ejmech.2017.03.058. Epub 2017 Mar 27.

Abstract

A PG-tb1 hapten from the West Beijing strains of Mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to CRM in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent T-dependent conjugate vaccine. The intermediate monoester can be easily purified and the degree of incorporation can be monitored by MALDI-TOF mass spectrometry. After administered systemically in mice without any adjuvant, the conjugate induced high antigen-specific IgG levels in serum. Furthermore, following the third immunization, significant antibody titers frequently exceeding 0.8 million were observed in the sera of mice vaccinated with PG-CRM conjugate which showed the potential for preparation of TB vaccine.

摘要

已通过应用丁烯二酸化学方法将来自结核分枝杆菌细胞壁的西北京株的 PG-tb1 半抗原有效地合成并连接到 CRM 上,作为带有连接子的碳水化合物,用于制备一种新型的糖结合蛋白,从而产生了一种有效的 T 依赖性结合疫苗。中间单酯可以很容易地纯化,并且可以通过 MALDI-TOF 质谱监测其结合程度。在没有任何佐剂的情况下全身给药后,该结合物在血清中诱导了高水平的抗原特异性 IgG。此外,在第三次免疫后,用 PG-CRM 结合物免疫的小鼠的血清中经常观察到超过 0.8 百万的抗体滴度,这表明其有用于制备结核疫苗的潜力。

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