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    Nucleic acids fragments and polypeptide fragments derived from M. tuberculosis
    5.
    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。

    Polynucleotide functionally coding for the LHP protein from Mycobacterium tuberculosis, its biologically active derivative fragments, as well as methods using the same
    7.
    发明授权
    Polynucleotide functionally coding for the LHP protein from Mycobacterium tuberculosis, its biologically active derivative fragments, as well as methods using the same 失效
    功能性编码结核分枝杆菌LHP蛋白的多核苷酸，其生物活性衍生物片段，以及使用其的方法

    公开(公告)号：US06436409B1

    公开(公告)日：2002-08-20

    申请号：US09116492

    申请日：1998-07-16

    申请人： Brigitte Gicquel ,  Francois-Xavier Berthet ,  Peter Andersen ,  Peter Birk Rasmussen

    发明人： Brigitte Gicquel ,  Francois-Xavier Berthet ,  Peter Andersen ,  Peter Birk Rasmussen

    IPC分类号： A61K3904

    CPC分类号： C12R1/19 ,  A61K38/00 ,  C07K14/35 ,  C07K2319/00 ,  C12N15/74 ,  Y10S435/863

    摘要： The present invention is directed to a polynucleotide carrying an open reading frame coding for an antigenic polypeptide from Mycobacterium tuberculosis, named lhp, which is placed under the control of its own regulation signals which are functional in mycobacteria, specially in mycobacteria belonging to the Mycobacterium tuberculosis complex and also in fast growing mycobacteria such as Mycobacterium smegmatis. The invention is also directed to the polypeptide LHP encoded by lhp and most preferably to suitable antigenic portions of LHP as well as to oligomeric polypeptides containing more than one unit of LHP or an antigenic portion of LHP. The invention concerns also immunogenic and vaccine compositions containing a polypeptide or an oligomeric polypeptide such as defined above, as well as antibodies directed specifically against such polypeptides that are useful as diagnostic reagents. In another embodiment, the present invention is directed to a polynucleotide carrying the natural regulation signals of lhp which is useful in order to express heterologous proteins in mycobacteria. Finally, the present invention is directed to oligonucleotides comprising at least 12 consecutive nucleotides from the regulation sequence of lhp which are useful as reagents for detecting the presence of Mycobacterium tuberculosis in a biological sample.

    摘要翻译： 本发明涉及携带编码来自结核分枝杆菌的抗原多肽的开放阅读框的多核苷酸，命名为lhp，其被置于其自身调节信号的控制下，其在分枝杆菌中是功能性的，特别是在属于结核分枝杆菌的分枝杆菌中 复合物以及快速生长的分枝杆菌如分枝杆菌（Mycobacterium smegmatis）。 本发明还涉及由lhp编码的多肽LHP，最优选地是LHP的合适抗原部分以及含有多于一个单位的LHP或LHP的抗原部分的寡聚多肽。 本发明还涉及含有如上定义的多肽或寡聚多肽的免疫原性和疫苗组合物，以及专门针对可用作诊断试剂的多肽的抗体。 在另一个实施方案中，本发明涉及携带lhp的天然调节信号的多核苷酸，其可用于在分枝杆菌中表达异源蛋白质。 最后，本发明涉及包含来自lhp调节序列的至少12个连续核苷酸的寡核苷酸，其可用作检测生物样品中结核分枝杆菌存在的试剂。

    Vaccines comprising TB10.4
    9.
    发明授权
    Vaccines comprising TB10.4 有权
    疫苗包含TB10.4

    公开(公告)号：US08557258B2

    公开(公告)日：2013-10-15

    申请号：US13221211

    申请日：2011-08-30

    申请人： Jes Dietrich ,  Claus Aagaard ,  Peter Andersen

    发明人： Jes Dietrich ,  Claus Aagaard ,  Peter Andersen

    IPC分类号： A61K39/00 ,  A61K39/38 ,  A61K39/02 ,  A61K39/04

    CPC分类号： A61K39/04 ,  A61K2039/545 ,  A61K2039/55516 ,  A61K2039/55561

    摘要： Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4+T cells expressing high levels of IFN-γ, TNF-α, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 μg, as well as 15 μg, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 μg increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.

    摘要翻译： 使用Ag85B-TB10.4和IC31®佐剂的组合进行疫苗接种，产生大量表达高水平IFN-γ，TNF-α和IL-2的多功能CD4 + T细胞。 这反过来又导致了结核病小鼠气溶胶攻击模型中结核分枝杆菌感染的重大保护。 疫苗的免疫原性及其抗TB感染的能力都高度依赖于抗原剂量。 因此，尽管5杯以及15杯的标准抗原剂量没有诱导对结核分枝杆菌的显着保护，但将剂量降低至0.5杯可将疫苗的免疫原性以及其保护功效提高到可比水平 到BCG接种的小鼠中观察到的。 因此，具有特定抗原剂量的IC31®佐剂可以诱导针对结核分枝杆菌的强烈的保护性Th1应答。

    Adjuvant combinations of liposomes and mycobacterial lipids for immunization compositions and vaccines
    10.
    发明授权
    Adjuvant combinations of liposomes and mycobacterial lipids for immunization compositions and vaccines 有权
    用于免疫组合物和疫苗的脂质体和分枝杆菌脂质的佐剂组合

    公开(公告)号：US08241610B2

    公开(公告)日：2012-08-14

    申请号：US13083385

    申请日：2011-04-08

    申请人： Else Marie Agger ,  Peter Andersen ,  Anja Olsen ,  Ida Rosenkrands

    发明人： Else Marie Agger ,  Peter Andersen ,  Anja Olsen ,  Ida Rosenkrands

    IPC分类号： A61K9/127 ,  A61B5/055

    CPC分类号： A61K39/04 ,  A61K2039/55555 ,  A61K2039/55594

    摘要： The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis BCG. The total lipid extract contains both apolar lipids, polar lipids, and lipids of intermediate polarity of which the apolar lipids were found to induce the most powerful immune responses. The total lipids may be extracted with chloroform/methanol and re-dissolved in water before the addition of surfactant. This preparation may be used to induce prominent cell-mediated immune responses in a mammal in order to combat pathogens, or as a treatment for cancer.

    摘要翻译： 本发明提供了由表面活性剂，即二甲基十八烷基溴化铵/氯化物（DDA）和牛分枝杆菌BCG的脂质提取物的组合组成的疫苗佐剂。 总脂质提取物包含非极性脂质，极性脂质和具有中性极性的脂质，其中发现非极性脂质诱导最强大的免疫应答。 总脂质可以用氯仿/甲醇萃取，并在加入表面活性剂之前再溶解在水中。 该制剂可用于诱导哺乳动物中突出的细胞介导的免疫应答以抵抗病原体，或用作癌症治疗。