Lee C K, Weltzin R, Thomas W D, Kleanthous H, Ermak T H, Soman G, Hill J E, Ackerman S K, Monath T P
OraVax, Inc., Cambridge, MA 02139, USA.
J Infect Dis. 1995 Jul;172(1):161-72. doi: 10.1093/infdis/172.1.161.
Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans.
幽门螺杆菌是一种革兰氏阴性螺旋菌,是慢性浅表性(B型)胃炎和消化性溃疡病的病因。幽门螺杆菌的脲酶在大肠杆菌中表达为无活性的重组蛋白,纯化后为分子量550 - 600 kDa、直径约12 nm的颗粒结构。口服5微克脲酶与适当的黏膜佐剂(如大肠杆菌的不耐热毒素),可保护60% - 100%的小鼠免受强毒力猫幽门螺杆菌的攻击。保护作用与抗脲酶分泌型IgA抗体水平相关。口服抗原与胃内给药效果相当或更佳。肠胃外注射抗原或胃内给予无佐剂的高剂量抗原可诱导血清IgG,但不产生IgA抗体,也不能提供保护。重组脲酶作为口服疫苗候选物,作为预防人类幽门螺杆菌引起的慢性胃十二指肠疾病的一种方法值得进一步研究。