Neisseria mutants, lipooligosaccharides and immunogenic compositions
    4.
    发明授权
    Neisseria mutants, lipooligosaccharides and immunogenic compositions 有权
    奈瑟氏球菌突变体,脂寡糖和免疫原性组合物

    公开(公告)号:US07807181B2

    公开(公告)日:2010-10-05

    申请号:US10508309

    申请日:2003-03-20

    摘要: Provided herein are mutant strains of Neisseria meningitidis which produce Kdo-free lipid A as well as the Kdo-free lipid A molecules and immunogenic compositions containing such Kdo-free lipid A molecules from a Neisseria strain containing a genetically stable mutation which inactivates a gene selected from the group consisting of genes encoding arabinose-5-phosphate isomerase, CMP-Kdo synthetase and CMP-Kdo transferase. N. meningitidis NMB206 is a specifically exemplified strain which harbors a stable insertion mutation in the gene (kpsF) encoding A5P isomerase; strain NMB-249 is a specifically exemplified strain with a stable insertion mutation in the gene (kdtA) encoding CMP-Kdo synthetase, and strain NMB259 is specifically exemplified strain with a stable insertion mutation in the gene (kdsB) encoding CMP-Kdo transferase. Also provided by the present invention are methods for the production of Lipid A flee of 3-keto-3-deoxyoctanoic acid using these genetically stable N. meningitidis mutants. Also describes is pYT250, a plasmid functional in neisseriae and in enterics such as Escherichia coli.

    摘要翻译: 本文提供脑膜炎奈瑟球菌的突变菌株,其产生不含Kdo的脂质A以及不含Kdo的脂质A分子和含有来自包含基因稳定突变的不含Kdo的脂质A分子的免疫脂质A分子的灭活组合,所述遗传稳定突变使选择的基因失活 来自编码阿拉伯糖-5-磷酸异构酶,CMP-Kdo合成酶和CMP-Kdo转移酶的基因组。 脑膜炎奈瑟球菌NMB206是在编码A5P异构酶的基因(kpsF)中具有稳定插入突变的特异性例证菌株; 菌株NMB-249是编码CMP-Kdo合成酶的基因(kdtA)中具有稳定插入突变的特异性例证菌株,并且菌株NMB259具体示例是在编码CMP-Kdo转移酶的基因(kdsB)中具有稳定插入突变的菌株。 本发明还提供了使用这些遗传稳定的脑膜炎奈瑟球菌突变体生产3-酮-3-脱氧辛酸脂质A的方法。 还描述了pYT250,一种在奈瑟氏菌中和在诸如大肠杆菌等肠道中功能的质粒。