公开(公告)号：US20050260232A1

公开(公告)日：2005-11-24

申请号：US11109056

申请日：2005-04-19

申请人： William Jacobs ,  Barry Bloom ,  Mary Hondalus ,  Samantha Sampson ,  Vasan Sambandamurthy

发明人： William Jacobs ,  Barry Bloom ,  Mary Hondalus ,  Samantha Sampson ,  Vasan Sambandamurthy

IPC分类号： C07K14/35 ,  C12N1/21 ,  A61K39/04

CPC分类号： C07K14/35 ,  A61K2039/51

摘要： Non-naturally occurring mycobacteria in the Mycobacterium tuberculosis complex are provided. These mycobacteria have a deletion of an RD1 region or a region controlling production of a vitamin, and exhibit attenuated virulence in a mammal when compared to the mycobacteria without the deletion. Also provided are non-naturally occurring mycobacteria that have a deletion of a region controlling production of lysine, and mycobacteria comprising two attenuating deletions. Vaccines comprising these mycobacteria are also provided, as are methods of protecting mammals from virulent mycobacteria using the vaccines. Also provided are methods of preparing these vaccines which include the step of deleting an RD1 region or a region controlling production of a vitamin or the amino acids leucine and lysine from a mycobacterium in the M. tuberculosis complex. Embodiments of these mycobacteria, vaccines and methods, encompassing mycobacteria comprising a leucine auxotrophy and a pantothenate auxotrophy, are also provided.

摘要翻译： 提供了结核分枝杆菌复合物中非天然存在的分枝杆菌。 与没有缺失的分枝杆菌相比，这些分枝杆菌具有RD1区域或控制维生素产生的区域的缺失，并且在哺乳动物中表现出减毒的毒力。 还提供了具有控制赖氨酸生产的区域缺失的非天然存在的分枝杆菌，以及包含两个减毒缺失的分枝杆菌。 还提供了包含这些分枝杆菌的疫苗，以及使用疫苗来保护哺乳动物免受有毒分枝杆菌的方法。 还提供了制备这些疫苗的方法，其包括在结核分枝杆菌复合物中从分枝杆菌中删除RD1区域或控制维生素或氨基酸亮氨酸和赖氨酸生产的区域的步骤。 还提供了包括亮氨酸营养缺陷型和泛酸营养缺陷型的分枝杆菌的这些分枝杆菌，疫苗和方法的实施方案。

公开(公告)号：US07758874B2

公开(公告)日：2010-07-20

申请号：US11109056

申请日：2005-04-19

申请人： William R. Jacobs, Jr. ,  Barry Bloom ,  Mary K. Hondalus ,  Samantha Sampson ,  Vasan Sambandamurthy

发明人： William R. Jacobs, Jr. ,  Barry Bloom ,  Mary K. Hondalus ,  Samantha Sampson ,  Vasan Sambandamurthy

IPC分类号： A61K39/04 ,  A61K49/00 ,  A61K39/00

CPC分类号： C07K14/35 ,  A61K2039/51

摘要： Non-naturally occurring mycobacteria in the Mycobacterium tuberculosis complex are provided. These mycobacteria have a deletion of an RD1 region or a region controlling production of a vitamin, and exhibit attenuated virulence in a mammal when compared to the mycobacteria without the deletion. Also provided are non-naturally occurring mycobacteria that have a deletion of a region controlling production of lysine, and mycobacteria comprising two attenuating deletions. Vaccines comprising these mycobacteria are also provided, as are methods of protecting mammals from virulent mycobacteria using the vaccines. Also provided are methods of preparing these vaccines which include the step of deleting an RD1 region or a region controlling production of a vitamin or the amino acids leucine and lysine from a mycobacterium in the M. tuberculosis complex. Embodiments of these mycobacteria, vaccines and methods, encompassing mycobacteria comprising a leucine auxotrophy and a pantothenate auxotrophy, are also provided.

摘要翻译： 提供了结核分枝杆菌复合物中非天然存在的分枝杆菌。 与没有缺失的分枝杆菌相比，这些分枝杆菌具有RD1区域或控制维生素产生的区域的缺失，并且在哺乳动物中表现出减毒的毒力。 还提供了具有控制赖氨酸生产的区域缺失的非天然存在的分枝杆菌，以及包含两个减毒缺失的分枝杆菌。 还提供了包含这些分枝杆菌的疫苗，以及使用疫苗来保护哺乳动物免受有毒分枝杆菌的方法。 还提供了制备这些疫苗的方法，其包括在结核分枝杆菌复合物中从分枝杆菌中删除RD1区域或控制维生素或氨基酸亮氨酸和赖氨酸生产的区域的步骤。 还提供了包括亮氨酸营养缺陷型和泛酸营养缺陷型的分枝杆菌的这些分枝杆菌，疫苗和方法的实施方案。

公开(公告)号：US20070202131A1

公开(公告)日：2007-08-30

申请号：US10542958

申请日：2004-01-23

申请人： William Jacobs ,  Tsungda Hsu ,  Vasan Sambandamurthy ,  Sheldon Morris ,  Stoyan Bardarov ,  Svetoslav Bardarvo

发明人： William Jacobs ,  Tsungda Hsu ,  Vasan Sambandamurthy ,  Sheldon Morris ,  Stoyan Bardarov ,  Svetoslav Bardarvo

IPC分类号： A61K39/04 ,  C12N1/21

CPC分类号： A61K39/04 ,  A61K2039/522

摘要： Methods of treating a mammal that is deficient in CD4+ and/or CD8+ lymphocytes are provided. The methods comprise inoculating the mammal with an attenuated mycobacterium in the M. tuberculosis complex. In these methods, the mycobacterium comprises two deletions, wherein a virulent mycobacterium in the M. tuberculosis complex having either deletion exhibits attenuated virulence. Use of these mycobacteria for the manufacture of a medicament for the treatment of mammals deficient in CD4+ and/or CD8+ lymphocytes is also provided.

摘要翻译： 提供了治疗缺乏CD4 +和/或CD8 +淋巴细胞的哺乳动物的方法。 所述方法包括在结核分枝杆菌复合物中用减毒的分枝杆菌接种哺乳动物。 在这些方法中，分枝杆菌包含两个缺失，其中具有任一缺失的结核分枝杆菌复合体中的有毒分枝杆菌表现出减毒的毒力。 还提供了这些分枝杆菌用于制备用于治疗缺乏CD4 +和/或CD8 +淋巴细胞的哺乳动物的药物的用途。

公开(公告)号：US07722861B2

公开(公告)日：2010-05-25

申请号：US10351452

申请日：2003-01-24

申请人： William R. Jacobs ,  Tsungda Hsu ,  Stoyan Bardarov ,  Svetoslav Bardarov, legal representative ,  Vasan Sambandamurthy

发明人： William R. Jacobs ,  Tsungda Hsu ,  Stoyan Bardarov ,  Vasan Sambandamurthy

IPC分类号： A01N63/00 ,  A61K48/00 ,  A61K39/04

CPC分类号： C12N9/93 ,  A61K39/00 ,  A61K2039/51 ,  C07K14/35 ,  C12N9/88 ,  C12Y401/01011 ,  C12Y603/02001

摘要： Non-naturally occurring mycobacteria in the Mycobacterium tuberculosis complex are provided. These mycobacteria have a deletion of an RD1 region or a region controlling production of a vitamin, and exhibit attenuated virulence in a mammal when compared to the mycobacteria without the deletion. Also provided are non-naturally occurring mycobacteria that have a deletion of a region controlling production of lysine, and mycobacteria comprising two attenuating deletions. Vaccines comprising these mycobacteria are also provided, as are methods of protecting mammals from virulent mycobacteria using the vaccines. Also provided are methods of preparing these vaccines which include the step of deleting an RD1 region or a region controlling production of a vitamin from a mycobacterium in the M. tuberculosis complex.

摘要翻译： 提供了结核分枝杆菌复合物中非天然存在的分枝杆菌。 与没有缺失的分枝杆菌相比，这些分枝杆菌具有RD1区域或控制维生素产生的区域的缺失，并且在哺乳动物中表现出减毒的毒力。 还提供了具有控制赖氨酸生产的区域缺失的非天然存在的分枝杆菌，以及包含两个减毒缺失的分枝杆菌。 还提供了包含这些分枝杆菌的疫苗，以及使用疫苗来保护哺乳动物免受有毒分枝杆菌的方法。 还提供了制备这些疫苗的方法，其包括在结核分枝杆菌复合物中从分枝杆菌中去除RD1区域或控制维生素维生素的区域的步骤。

公开(公告)号：US08084041B2

公开(公告)日：2011-12-27

申请号：US10542958

申请日：2004-01-23

申请人： William R. Jacobs, Jr. ,  Tsungda Hsu ,  Vasan Sambandamurthy ,  Sheldon Morris ,  Stoyan Bardarov ,  Svetoslav Bardarov, legal representative

发明人： William R. Jacobs, Jr. ,  Tsungda Hsu ,  Vasan Sambandamurthy ,  Sheldon Morris ,  Stoyan Bardarov

IPC分类号： A61K39/04 ,  A61K39/02 ,  C07H21/04

CPC分类号： A61K39/04 ,  A61K2039/522

摘要： Methods of treating a mammal that is deficient in CD4+ and/or CD8+ lymphocytes are provided. The methods comprise inoculating the mammal with an attenuated mycobacterium in the M. tuberculosis complex. In these methods, the mycobacterium comprises two deletions, wherein a virulent mycobacterium in the M. tuberculosis complex having either deletion exhibits attenuated virulence. Use of these mycobacteria for the manufacture of a medicament for the treatment of mammals deficient in CD4+ and/or CD8+ lymphocytes is also provided.

摘要翻译： 提供了治疗缺乏CD4 +和/或CD8 +淋巴细胞的哺乳动物的方法。 所述方法包括在结核分枝杆菌复合物中用减毒的分枝杆菌接种哺乳动物。 在这些方法中，分枝杆菌包含两个缺失，其中具有任一缺失的结核分枝杆菌复合体中的有毒分枝杆菌表现出减毒的毒力。 还提供了这些分枝杆菌用于制备用于治疗缺乏CD4 +和/或CD8 +淋巴细胞的哺乳动物的药物的用途。