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    Nucleic acids fragments and polypeptide fragments derived from M. tuberculosis
    1.
    发明授权
    Nucleic acids fragments and polypeptide fragments derived from M. tuberculosis 失效
    衍生自结核分枝杆菌的核酸片段和多肽片段

    公开(公告)号：US06641814B1

    公开(公告)日：2003-11-04

    申请号：US09050739

    申请日：1998-03-30

    申请人： Peter Andersen ,  Rikke Nielsen ,  Thomas Oettinger ,  Peter Birk Rasmussen ,  Ida Rosenkrands ,  Karin Weldingh ,  Walter Florio

    发明人： Peter Andersen ,  Rikke Nielsen ,  Thomas Oettinger ,  Peter Birk Rasmussen ,  Ida Rosenkrands ,  Karin Weldingh ,  Walter Florio

    IPC分类号： A61K3902

    CPC分类号： C07K14/35 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/51 ,  C07K2319/00

    摘要： The present invention is based on the identification and characterization of a number of M. tuberculosis derived novel proteins and protein fragments (SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 17-23, 42, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72-86, 88, 90, 92, 94, 141, 143, 145, 147, 149, 151, 153, and 168-171). The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as vaccines and skin test reagents containing the polypeptides. Another part of the invention is based on the surprising discovery that fusions between ESAT-6 and MPT59 are superior immunogens compared to each of the unfused proteins, respectively.

    摘要翻译： 本发明基于许多结核分枝杆菌来源的新蛋白质和蛋白质片段的鉴定和表征（SEQ ID NO：2,4,6,8,10,12,14,16,17-23,42， 48，50，52，54，56，58，60，62，64，66，68，70，72-86，88，90，92，94，141，143，145，147，149，151，153， 和168-171）。 本发明涉及多肽及其免疫活性片段，编码它们的基因，免疫组合物如疫苗和含有多肽的皮肤试验试剂。 本发明的另一部分是基于惊人的发现，即分别与每种未融合的蛋白质相比，ESAT-6和MPT59之间的融合是优越的免疫原。

    Specific epitope based immunological diagnosis of tuberculosis
    4.
    发明申请
    Specific epitope based immunological diagnosis of tuberculosis 有权
    特异性表位基因免疫诊断结核病

    公开(公告)号：US20060115847A1

    公开(公告)日：2006-06-01

    申请号：US11268959

    申请日：2005-11-08

    申请人： Peter Andersen ,  Inger Brock ,  Karin Weldingh

    发明人： Peter Andersen ,  Inger Brock ,  Karin Weldingh

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： G01N33/6812 ,  C07K14/35 ,  G01N33/505 ,  G01N33/5695

    摘要： The currently used method for immunological diagnosis of tuberculosis infection, the tuberculin skin test, is problematic for a number of reasons; it has low specificity in BCG vaccinated individuals, a high interobserver variance and requires skill to be read and interpreted. Furthermore it requires an extra visit to the clinic to have the test read. Both people vaccinated with BCG and those exposed to non-tuberculosis mycobacteria give a positive skin test result similar to that seen in a TB infected individual. This also applies for purified protein derivative (PPD) when used in a blood cell based test. The present invention discloses the development of an immunological TB diagnostic tool based on a combination of epitopes from proteins encoded by regions of the M. Tuberculosis (M. tub.) genome, that are not present in the BCG vaccine strain or in the most common non-tuberculosis mycobacteria. Four recently characterized proteins with this diagnostic potential were selected. Peptides from these proteins were tested one by one with peripheral blood mononuclear cells from microscopy or culture confirmed TB patients as well as from healthy BCG vaccinated controls. Some combinations of peptides showed a sensitivity level comparable to the level seen with the two wellknown M. tuberculosisspecific proteins ESAT 6 and CFP 10. An epitope combination with these peptides combined with ESAT 6 and CFP 10 gave a sensitivity of 93%, representing a raise in sensitivity of about 26-33% compared to using ESAT6 or CFP 10 alone. The results from a panel of TB patients, using a collection of the new specific epitopes clearly demonstrates, that addition of other specific epitopes to the already known specific antigens, increases the sensitivity of a diagnostic assay based on cell mediated immune response.

    摘要翻译： 目前使用的结核菌感染免疫诊断方法，结核菌素皮肤试验，有其原因有问题; 它在BCG接种个体中具有低特异性，具有高的观察者间差异，并且需要阅读和解释技能。 此外，还需要额外访问诊所以进行测试。 接种BCG的人和暴露于非结核分枝杆菌的两个人都能获得与TB感染个体相似的阳性皮肤试验结果。 当用于基于血细胞的试验中时，这也适用于纯化的蛋白质衍生物（PPD）。 本发明公开了一种免疫结核病诊断工具的开发，该工具基于由结核分枝杆菌（M. tub。）（M. tub。）基因组区域编码的蛋白质的表位的组合，其不存在于BCG疫苗株中或最常见 非结核分枝杆菌。 选择了具有该诊断潜力的四种最近鉴定的蛋白质。 使用来自显微镜或培养物确认的TB患者以及来自健康的BCG接种对照的外周血单核细胞逐个测试来自这些蛋白质的肽。 肽的一些组合显示出与两种已知的结核分枝杆菌特异性蛋白质ESAT 6和CFP 10所见的水平相当的灵敏度水平。与这些肽结合ESAT 6和CFP 10的表位结合产生93％的灵敏度，表示升高 与单独使用ESAT6或CFP 10相比，灵敏度约为26-33％。 使用新的特异性表位的一组结核病患者的结果清楚地表明，已知的特异性抗原的其他特异性表位的添加增加了基于细胞介导的免疫应答的诊断测定的灵敏度。

    Specific epitope based immunological diagnosis of tuberculosis
    5.
    发明授权
    Specific epitope based immunological diagnosis of tuberculosis 有权
    特异性表位基因免疫诊断结核病

    公开(公告)号：US07838013B2

    公开(公告)日：2010-11-23

    申请号：US11268959

    申请日：2005-11-08

    申请人： Peter Andersen ,  Inger Brock ,  Karin Weldingh

    发明人： Peter Andersen ,  Inger Brock ,  Karin Weldingh

    IPC分类号： A61K39/04 ,  A61K39/00 ,  C12Q1/00

    CPC分类号： G01N33/6812 ,  C07K14/35 ,  G01N33/505 ,  G01N33/5695

    摘要： The currently used method for immunological diagnosis of tuberculosis infection, the tuberculin skin test, is problematic for a number of reasons; it has low specificity in BCG vaccinated individuals, a high interobserver variance and requires skill to be read and interpreted. Furthermore it requires an extra visit to the clinic to have the test read. Both people vaccinated with BCG and those exposed to non-tuberculosis mycobacteria give a positive skin test result similar to that seen in a TB infected individual. This also applies for purified protein derivative (PPD) when used in a blood cell based test. The present invention discloses the development of an immunological TB diagnostic tool based on a combination of epitopes from proteins encoded by regions of the M. tuberculosis (M. tub.) genome, that are not present in the BCG vaccine strain or in the most common non-tuberculosis mycobacteria.

    摘要翻译： 目前使用的结核菌感染免疫诊断方法，结核菌素皮肤试验，有其原因有问题; 它在BCG接种个体中具有低特异性，具有高的观察者间差异，并且需要阅读和解释技能。 此外，还需要额外访问诊所以进行测试。 接种BCG的人和暴露于非结核分枝杆菌的两个人都能获得与TB感染个体相似的阳性皮肤试验结果。 当用于基于血细胞的试验中时，这也适用于纯化的蛋白质衍生物（PPD）。 本发明公开了一种免疫结核病诊断工具的开发，该工具基于由结核分枝杆菌（M.Bob。）基因组区域编码的蛋白质的表位的组合，其不存在于BCG疫苗株中或最常见 非结核分枝杆菌。