公开(公告)号：US07838014B2

公开(公告)日：2010-11-23

申请号：US10523044

申请日：2003-07-31

申请人： Ralph Biemans ,  Philippe Denoel ,  Christiane Feron ,  Carine Goraj ,  Jan Poolman ,  Vincent Weynants

发明人： Ralph Biemans ,  Philippe Denoel ,  Christiane Feron ,  Carine Goraj ,  Jan Poolman ,  Vincent Weynants

IPC分类号： A61K39/05

CPC分类号： A61K39/095 ,  A61K39/102 ,  A61K39/1045 ,  A61K2039/521 ,  A61K2039/55505 ,  A61K2039/55516 ,  A61K2039/55572 ,  A61K2039/55577 ,  A61K2039/70 ,  C07K14/22 ,  Y02A50/396

摘要： The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and Opc, and PorA and OpA and OpC. Alternatively, or in addition, lgtB− is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS in Neisseria vaccine compositions. Bleb vaccines derived from lgtB− and capsular polysaccharide deficient meningococcal mutants are further described; as are advantageous methods of making bleb preparations where LOS is to be retained as an important antigen.

摘要翻译： 本发明涉及奈瑟氏球菌疫苗组合物的领域，它们的制造以及这些组合物在医药中的用途。 更具体地说，本发明涉及制备新型工程化脑膜炎球菌菌株的方法，其更适合于产生奈司菌素，特别是脑膜炎球菌，外膜囊泡（或气泡）疫苗。 还基于使用已经变得更安全和/或更有效地用于人类受试者的新型LOS亚单位或脑膜炎球菌外膜囊泡（或泡沫）疫苗来描述有利的方法和疫苗产品。 描述了基因下调的组合，例如PorA和OpA，PorA和OpC，OpA和Opc，以及PorA和OpA和OpC。 或者或另外，lgtB-被证明是用于在奈瑟氏球菌疫苗组合物中有效和安全地使用L3和/或L2 LOS的最佳突变。 进一步描述衍生自lgtB-和荚膜多糖缺乏脑膜炎球菌突变体的Bleb疫苗; 制备其中保留LOS作为重要抗原的泡制剂的有利方法也是如此。

公开(公告)号：US20060051379A1

公开(公告)日：2006-03-09

申请号：US10523044

申请日：2003-07-31

申请人： Ralph Biemans ,  Philippe Denoel ,  Christiane Feron ,  Carine Goraj ,  Jan Poolman ,  Vincent Weynants

发明人： Ralph Biemans ,  Philippe Denoel ,  Christiane Feron ,  Carine Goraj ,  Jan Poolman ,  Vincent Weynants

IPC分类号： A61K39/095 ,  C12N1/21 ,  C07K14/22

CPC分类号： A61K39/095 ,  A61K39/102 ,  A61K39/1045 ,  A61K2039/521 ,  A61K2039/55505 ,  A61K2039/55516 ,  A61K2039/55572 ,  A61K2039/55577 ,  A61K2039/70 ,  C07K14/22 ,  Y02A50/396

摘要： The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and Opc, and PorA and OpA and OpC. Alternatively, or in addition, lgtB− is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS in Neisseria vaccine compositions. Bleb vaccines derived from lgtB− and capsular polysaccharide deficient meningococcal mutants are further described; as are advantageous methods of making bleb preparations where LOS is to be retained as an important antigen.

摘要翻译： 本发明涉及奈瑟氏球菌疫苗组合物的领域，它们的制造以及这些组合物在医药中的用途。 更具体地说，本发明涉及制备新型工程化脑膜炎球菌菌株的方法，其更适合于产生奈司菌素，特别是脑膜炎球菌，外膜囊泡（或气泡）疫苗。 还基于使用已经变得更安全和/或更有效地用于人类受试者的新型LOS亚单位或脑膜炎球菌外膜囊泡（或泡沫）疫苗来描述有利的方法和疫苗产品。 描述了基因下调的组合，例如PorA和OpA，PorA和OpC，OpA和Opc，以及PorA和OpA和OpC。 或者或另外，lgtB 被证明是用于在奈瑟氏球菌疫苗组合物中有效和安全地使用L3和/或L2 LOS的最佳突变。 进一步描述衍生自lgtB 和荚膜多糖缺乏脑膜炎球菌突变体的Bleb疫苗; 制备其中保留LOS作为重要抗原的泡制剂的有利方法也是如此。

公开(公告)号：US20070231876A1

公开(公告)日：2007-10-04

申请号：US11575676

申请日：2005-09-20

申请人： Ralph Biemans ,  Carine Goraj ,  Emmanuel Mertens ,  Anne Vandercammen

发明人： Ralph Biemans ,  Carine Goraj ,  Emmanuel Mertens ,  Anne Vandercammen

IPC分类号： C12N1/20

CPC分类号： C07K14/3156 ,  A61K39/00 ,  A61K39/092 ,  A61K2039/6087 ,  C07K1/1136 ,  C07K14/315

摘要： The present application relates to a process for purification of a bacterial cytolysin comprising the steps of a) growing a culture of cells expressing bacterial cytolysin, b) mechanically breaking the culture of cells to form an extract, c) prefiltering the extract, d) binding soluble aggregated bacterial cytolysin contained in the extract in the presence of detergent to a hydrophobic interaction chromatography material under high salt (preferably 0.6-2M salt) conditions, and e) eluting bacterial cytolysin in the presence of detergent under low salt (preferably 0-0.2M salt) conditions.

摘要翻译： 本申请涉及细菌细胞溶解素的纯化方法，其包括以下步骤：a）培养表达细菌细胞溶解素的细胞的培养物，b）机械破碎细胞培养物以形成提取物，c）预抽提物，d）结合 在高盐（优选0.6-2M盐））条件下，在洗涤剂存在下，提取物中包含的可溶性聚集细菌细胞溶解素至疏水相互作用层析材料，以及e）在洗涤剂存在下，在低盐下（优选0-0.2 M盐）条件。