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    Hybrid LT-A/CT-B holotoxin for use as an adjuvant
    2.
    发明授权
    Hybrid LT-A/CT-B holotoxin for use as an adjuvant 失效
    混合型LT-A / CT-B全毒素用作佐剂

    公开(公告)号：US07063852B2

    公开(公告)日：2006-06-20

    申请号：US10276844

    申请日：2001-05-21

    申请人： John D. Clements

    发明人： John D. Clements

    IPC分类号： A61K39/116

    CPC分类号： A61K39/00 ,  A61K39/08 ,  A61K39/39 ,  A61K2039/541 ,  A61K2039/55544 ,  Y02A50/464 ,  Y02A50/472 ,  Y02A50/476

    摘要： The present invention provides a novel composition which is a hybrid heat labile enterotoxin comprising the A-subunit of the heat labile toxin of Escherichia coli (LT-A) and the B-subunit of the cholera enterotoxin of Vibrio cholerae (CT-B). The hybrid toxin is designated LT-A/CT-B. The LT-A subunit, the CT-B subunit, or both subunits of the hybrid toxin may be mutant subunits, e.g., differing from wild-type subunits by amino acid substitutions, deletions or additions. Also provided are methods of using the novel LT-A/CT-B comprising compositions of the invention as adjuvants for vaccines, methods of making the LT-A/CT-B hybrid holotoxin, and kits.

    摘要翻译： 本发明提供了一种新型组合物，其是包含大肠杆菌（LT-A）的热不稳定毒素的A亚单位和霍乱弧菌（CT-B）的霍乱肠毒素的B亚单位的杂合热不稳定肠毒素。 杂交毒素称为LT-A / CT-B。 杂交毒素的LT-A亚基，CT-B亚基或两个亚基可以是突变体亚基，例如，通过氨基酸取代，缺失或添加与野生型亚基不同。 还提供了使用包含本发明组合物的新型LT-A / CT-B作为疫苗佐剂，制备LT-A / CT-B杂合全毒素的方法和试剂盒的方法。

    Oral immunization with transgenic plants
    3.
    发明授权
    Oral immunization with transgenic plants 失效
    用转基因植物进行口服免疫

    公开(公告)号：US06395964B1

    公开(公告)日：2002-05-28

    申请号：US08817906

    申请日：1997-08-04

    申请人： Charles J. Arntzen ,  Hugh S. Mason ,  Haq A. Tariq ,  John D. Clements

    发明人： Charles J. Arntzen ,  Hugh S. Mason ,  Haq A. Tariq ,  John D. Clements

    IPC分类号： C12N504

    CPC分类号： C07K14/28 ,  A61K39/04 ,  A61K39/08 ,  A61K39/39 ,  A61K2039/53 ,  A61K2039/542 ,  A61K2039/55544 ,  C07K14/245 ,  C12N15/8258

    摘要： The oral antigens and adjuvants of the present invention are produced in transgenic plants and then administered through the consumption of the transgenic plant. DNA sequences both natural and synthetic encoding for the expression of immunogenic agents which are capable of causing an immune response in animals when fed in edible plants, plant tissues, or derived plant materials are constructed, and plants transformed for stable or transient expression in plant cells. The present invention provides the first known functional method for immunizing animals via transgenic plants, where the plants express bacterial antigens that act as both immunogen and adjuvants when the transgenic plant material expressing the antigens is fed to animals.

    摘要翻译： 本发明的口服抗原和佐剂在转基因植物中产生，然后通过消耗转基因植物施用。 构建天然和合成编码免疫原性表达的DNA序列，其在饲喂可食用植物，植物组织或衍生植物材料时能够在动物中引起免疫应答，植物转化用于在植物细胞中稳定或瞬时表达 。 本发明提供了用于通过转基因植物免疫动物的第一已知功能方法，其中当将表达抗原的转基因植物材料供给动物时，植物表达作为免疫原和佐剂的细菌抗原。

    Double mutant enterotoxin for use as an adjuvant
    4.
    发明授权
    Double mutant enterotoxin for use as an adjuvant 失效
    双突变肠毒素用作佐剂

    公开(公告)号：US6033673A

    公开(公告)日：2000-03-07

    申请号：US44064

    申请日：1998-03-18

    申请人： John D. Clements

    发明人： John D. Clements

    IPC分类号： A61K39/39 ,  A61P37/04 ,  C07K14/245 ,  G01N33/569 ,  A61K39/02 ,  A61K39/108 ,  A61K45/00 ,  A61K39/00

    CPC分类号： G01N33/56916 ,  A61K39/39 ,  C07K14/245 ,  A61K2039/542 ,  A61K2039/55544 ,  Y10S424/832 ,  Y10S514/885

    摘要： The present invention is directed towards a novel composition which is a genetically distinct mutant of E. coli heat-labile enterotoxin (LT). Specifically, the mutant LT designated LT(R192G/L211A) is modified by two amino acid substitutions, i.e., the arginine at amino acid position 192 is replaced by glycine and the leucine at amino acid position 211 is replaced by alanine. The invention relates to compositions and methods for use of the novel double mutant of LT as an adjuvant.

    摘要翻译： 本发明涉及一种新的组合物，其是大肠杆菌热不稳定肠毒素（LT）的遗传上不同的突变体。 具体地，通过两个氨基酸取代修饰LT（R192G / L211A）的突变体LT，即氨基酸位置192处的精氨酸被甘氨酸代替，氨基酸位置211处的亮氨酸被丙氨酸替代。 本发明涉及使用LT的新型双突变体作为佐剂的组合物和方法。

    Composition of a novel immunogen for protection against diarrheal disease caused by enterotoxigenic Escherichia coli
    8.
    发明授权
    Composition of a novel immunogen for protection against diarrheal disease caused by enterotoxigenic Escherichia coli 失效
    用于防止肠毒素性大肠杆菌引起的腹泻病的新型免疫原的组成

    公开(公告)号：US4411888A

    公开(公告)日：1983-10-25

    申请号：US403751

    申请日：1982-06-03

    申请人： Frederick A. Klipstein ,  Richard E. Engert ,  John D. Clements

    发明人： Frederick A. Klipstein ,  Richard E. Engert ,  John D. Clements

    IPC分类号： A61K39/106 ,  A61K39/108

    CPC分类号： A61K39/107 ,  A61K39/0258 ,  A61K2039/6037

    摘要： There is disclosed a novel immunogen which can be used for immunological protection against acute diarrheal disease caused by enterotoxigenic strains of Escherichia coli. The novel immunogen is provided by cross-linking the E. coli heat-stable enterotoxin with the E. coli heat-labile enterotoxin (either the complete holotoxin or just the B subunit of this toxin) by a conjugation process in the presence of a conjugating agent, typically the water soluble carbodiimide, 1-ethyl-3-(3-diamethylaminopropyl) carbodiimide. This results in a unique new molecule in that the toxic properties of each individual toxin are greatly reduced, the heat-labile toxin (or its B subunit) retains its antigenicity, and the heat-stable toxin acquires immunogenicity as a function of the reaction. Immunization with the cross-linked immunogen provides immunological protection in mammals against water secretion induced by strains of E. coli which produce the heat-labile or heat-stable enterotoxins, either singly or together.

    摘要翻译： PCT No.PCT / US82 / 00763 Sec。 371日期1982年6月3日 102（e）1982年6月3日PCT PCT 1982年6月3日PCT公布。 第WO83 / 00018号公报 日期：1983年1月6日。公开了一种新型免疫原，其可用于针对由大肠杆菌的肠毒素菌株引起的急性腹泻病的免疫保护。 新型免疫原是通过共轭过程在大肠杆菌热不稳定肠毒素（完全全毒素或该毒素的B亚基）上交联大肠杆菌热稳定肠毒素来提供的 通常为水溶性碳二亚胺，1-乙基-3-（3-二甲基氨基丙基）碳二亚胺。 这导致独特的新分子，因为各种毒素的毒性大大降低，热不稳定毒素（或其B亚基）保持其抗原性，并且热稳定毒素作为反应的函数获得免疫原性。 使用交联的免疫原免疫在哺乳动物中提供针对产生热不稳定或热稳定的肠毒素的大肠杆菌菌株诱导的水分泌的单独或一起的免疫保护。

    Production of the E. coli LT-B enterotoxin subunit
    10.
    发明授权
    Production of the E. coli LT-B enterotoxin subunit 失效
    生产大肠杆菌LT-B肠毒素亚基

    公开(公告)号：US5308835A

    公开(公告)日：1994-05-03

    申请号：US018652

    申请日：1993-02-17

    申请人： John D. Clements

    发明人： John D. Clements

    IPC分类号： C07K14/245 ,  C07K14/28 ,  C07K16/12 ,  G01N33/569 ,  A61K39/108 ,  A61K39/02 ,  C07K15/04

    CPC分类号： C07K14/28 ,  C07K14/245 ,  C07K16/1232 ,  C07K16/1239 ,  G01N33/56916 ,  Y10S530/806

    摘要： Methods and compositions are provided for the cloning and expression of genes coding for the non-toxic subunit of the heat-labile enterotoxin (LT-B) of E. coli. The LT-B thus produced may be formulated for use as an immunogen in vaccines. Specific antibodies produced by this invention may be used in diagnostic tests for the detection of Vibrio cholerae or LT positive enterotoxigenic E. coli. The antibodies of this invention may further be formulated into passive vaccines for the prophylactic or therapeutic protection of human beings or other mammalian species against diarrheal diseases caused by Vibrio cholerae or by the LT positive enterotoxigenic E. coli or other bacteria.

    摘要翻译： 提供了用于克隆和表达编码大肠杆菌的热不稳定肠毒素（LT-B）的无毒亚基的基因的方法和组合物。 这样制备的LT-B可以配制成用作疫苗中的免疫原。 本发明产生的特异性抗体可用于检测霍乱弧菌或LT阳性致肠毒性大肠杆菌的诊断试验。 本发明的抗体可以进一步配制成用于预防或治疗保护人类或其他哺乳动物物种的针对由霍乱弧菌引起的腹泻疾病或由LT阳性致肠毒性大肠杆菌或其它细菌引起的抗体。