Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG
    5.
    发明授权
    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG 有权
    改良的ESAT-6分子和改良的牛分枝杆菌BCG的疫苗株

    公开(公告)号:US08398991B2

    公开(公告)日:2013-03-19

    申请号:US11455929

    申请日:2006-06-20

    IPC分类号: A61K39/02

    摘要: A genetically modified strain of M. tuberculosis or Mycobacterium bovis BCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Y51, Q55, Q56, N66, M83, V90, M93, or F94 in SEQ ID NO:1; or at least one mutation at Q3, F7 A13, L27, W42, G44, Y50, Q54, N65, N67, M82, V89, M92, or F93 in SEQ ID NO:2, or a deletion at the terminal end of less than 20 amino acids. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, AI4R, L28A, L29S, W43R, G45T, Q55I, Q56A, N66I, N67A, M83I, V90R, M93T, or F94Q in SEQ ID NO:1, and Q3L, F7I, A13R, L27A, L28S, W42R, Q44T, Q54I, N65I, M82I, V89R, M92T, and F93Q in SEQ ID NO:2. Similarly, the genetically modified strain may also secrete ESAT-6 with a hexa-histidine tag, tetra-cysteine tag, or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

    摘要翻译: 提供结核分枝杆菌或牛分枝杆菌BCG的遗传修饰菌株,其中所述遗传修饰菌株包含至少一个包含SEQ ID NO:1,SEQ ID NO:2或两者的经修饰的序列,或在T2处具有至少一个突变, SEQ ID NO:1中的Q4,F8,A14,L28,L29,W43,G45,Y51,Q55,Q56,N66,M83,V90,M93或F94; 或SEQ ID NO:2中的Q3,F7A13,L27,W42,G44,Y50,Q54,N65,N67,M82,V89,M92或F93的至少一个突变,或末端的缺失小于 20个氨基酸。 在优选实施方案中,突变是SEQ ID NO:1中的T2H,Q4L,F8I,AI4R,L28A,L29S,W43R,G45T,Q55I,Q56A,N66I,N67A,M83I,V90R,M93T或F94Q中的至少一种 ,以及SEQ ID NO:2中的Q3L,F7I,A13R,L27A,L28S,W42R,Q44T,Q54I,N65I,M82I,V89R,M92T和F93Q。 类似地,遗传修饰的菌株也可以分泌具有六组氨酸标签,四半胱氨酸标签或FLAG标签的ESAT-6,GFP-融合物或C末端的短截短小于20个氨基酸 。

    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG
    6.
    发明申请
    Modified ESAT-6 molecules and improved vaccine strains of Mycobacterium bovis BCG 有权
    改良的ESAT-6分子和改良的牛分枝杆菌BCG的疫苗株

    公开(公告)号:US20070009547A1

    公开(公告)日:2007-01-11

    申请号:US11455929

    申请日:2006-06-20

    IPC分类号: A61K39/04 C12N1/21

    摘要: A genetically modified strain of M. tuberculosis or Mycobacterium bovis BCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Q55, Q56, N66, M83, V90, M93, or F94. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, A14R, L28A, L29S, W43R, G45T, Y51, Q55I, Q56A, N66I, N66A, M83I, V90R, M93T, or F94Q. Similarly, the genetically modified strain may also secrete ESAT-6 with a a histidine tag, tetra-cysteine tag or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

    摘要翻译: 提供结核分枝杆菌或牛分枝杆菌BCG的遗传修饰菌株,其中所述遗传修饰菌株包含至少一个包含SEQ ID NO:1,SEQ ID NO:2或两者的经修饰的序列,或在T2处具有至少一个突变, Q4,F8,A14,L28,L29,W43,G45,Q55,Q56,N66,M83,V90,M93或F94。 在优选的实施方案中,突变是T2H,Q4L,F8I,A14R,L28A,L29S,W43R,G45T,Y51,Q55I,Q56A,N66I,N66A,M83I,V90R,M93T或F94Q中的至少一种。 类似地,遗传修饰的菌株也可以在小于20个氨基酸的C末端分泌具有组氨酸标签,四半胱氨酸标签或FLAG标签,GFP融合物或短截短的ESAT-6。