公开(公告)号：US20050142149A1

公开(公告)日：2005-06-30

申请号：US11040661

申请日：2005-01-21

申请人： Helen Crooke ,  Enda Clarke ,  Paul Everest ,  Gordon Dougan ,  David Holden ,  Jacqueline Shea ,  Robert Feldman

发明人： Helen Crooke ,  Enda Clarke ,  Paul Everest ,  Gordon Dougan ,  David Holden ,  Jacqueline Shea ,  Robert Feldman

IPC分类号： G01N33/50 ,  A61K35/74 ,  A61K38/00 ,  A61K39/00 ,  A61K39/108 ,  A61K48/00 ,  A61P31/04 ,  C07K14/245 ,  C07K14/345 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/31 ,  C12P21/02 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/15 ,  A61K39/02 ,  C12N15/74

CPC分类号： C07K14/245 ,  A61K38/00 ,  A61K39/00 ,  Y10S436/815 ,  Y10S930/30 ,  Y10S930/31

摘要： The present invention is based on the identification of a series of virulence genes in E. coli K1, the products of which may be implicated in the pathogenicity of the organisms. The identification of the genes allows them, or their expressed products, to be used in a number of ways to treat infection.

公开(公告)号：US06905691B1

公开(公告)日：2005-06-14

申请号：US09591447

申请日：2000-06-09

申请人： Steven Neville Chatfield ,  Gordon Dougan ,  Mark Sydenham

发明人： Steven Neville Chatfield ,  Gordon Dougan ,  Mark Sydenham

IPC分类号： C12N1/20 ,  A66K39/02 ,  A61K39/295 ,  A61K39/10 ,  A61K39/102 ,  A61K39/108

CPC分类号： A61K39/0275 ,  A61K2039/522 ,  A61K2039/542 ,  C12N1/20 ,  Y02A50/482 ,  Y02A50/484

摘要： The invention relates to a vaccine comprising a bacterium attenuated by a non-reverting mutation in a gene encoding a protein which promotes folding of extracytoplasmic proteins. Such mutations were initially identified as being useful in vaccines from a bank of randomly inserted, transposon mutants in which attenuation was determined as a reduction in virulence of the organism in the mouse model of infection. Site directed mutation of the gene results in a strain which shows at least 4 logs of attenuation when delivered both orally and intravenously. Animals vaccinated with such a strain are protected against subsequent challenge with the parent wild type strain. Finally, heterologous antigens such as the non-toxic and protective, binding domain from tetanus toxin, fragment C, can be delivered via the mucosal immune system using such strains of bacteria. This results in the induction of a fully protective immune response to subsequent challenge with native tetanus toxin.

摘要翻译： 本发明涉及一种疫苗，其包含在编码促进胞质内蛋白质折叠的蛋白质的基因中通过非回复突变减毒的细菌。 这些突变最初被鉴定为可用于来自随机插入的转座子突变体的疫苗中，其中衰减被确定为感染小鼠模型中生物的毒力的降低。 该基因的位点定向突变导致在口服和静脉内递送时显示至少4个原木衰减的菌株。 用这种菌株接种疫苗的动物被保护免受随后的亲本野生型菌株的攻击。 最后，异源抗原如破伤风毒素（片段C）的无毒和保护性结合结构域可以通过使用这种细菌菌株的粘膜免疫系统递送。 这导致诱导完全保护性的免疫应答，随后用天然破伤风毒素进行攻击。

公开(公告)号：US06680182B1

公开(公告)日：2004-01-20

申请号：US08379611

申请日：1995-07-21

申请人： Mohammed Anjam Khan ,  Bernardo Villarreal-Ramos ,  Carlos Estenio Hormaeche ,  Steven Neville Chatfield ,  Gordon Dougan

发明人： Mohammed Anjam Khan ,  Bernardo Villarreal-Ramos ,  Carlos Estenio Hormaeche ,  Steven Neville Chatfield ,  Gordon Dougan

IPC分类号： C12N1509

CPC分类号： C12N15/62 ,  A61K39/00 ,  C07K14/005 ,  C07K14/33 ,  C07K2319/00 ,  C07K2319/23 ,  C07K2319/40 ,  C07K2319/55 ,  C12N9/1088 ,  C12N2710/16622 ,  C12N2710/20022 ,  C12N2740/15022 ,  C12N2770/32122 ,  Y02A50/412 ,  Y02A50/423 ,  Y02A50/464 ,  Y02A50/466 ,  Y02A50/472 ,  Y02A50/484

摘要： The invention provides a DNA molecule comprising a promoter sequence operably linked to a DNA sequence encoding first and second proteins linked by a hinge region wherein in that the promoter sequence can be one having activity which is induced in response to a change in the surrounding environment and the first protein can be Tetanus toxin C fragment or one or more epitopes thereof. The invention also provides intermediate molecules having a promoter operably linked to a DNA sequence encoding a first antigenic sequence and a hinge region, and at or adjacent the 3′-end thereof one or more restriction sites for the introduction of a second anti-genic sequence. In addition, the invention provides replicable expression vectors containing the DNA fusion proteins expressed therefrom, bacterial transformed with the vectors and the use of the bacteria, in vaccines.

摘要翻译： 本发明提供了一种DNA分子，其包含与编码由铰链区连接的第一和第二蛋白质的DNA序列可操作地连接的启动子序列，其中启动子序列可以是具有响应于周围环境变化而诱导的活性的序列， 第一种蛋白质可以是破伤风毒素C片段或其一个或多个表位。 本发明还提供具有可操作地连接到编码第一抗原序列和铰链区的DNA序列的启动子的中间分子，并且在其3'端或其邻近位置具有用于引入第二抗基因序列的一个或多个限制性位点 。 此外，本发明提供了在疫苗中含有由其表达的DNA融合蛋白，用载体转化的细菌和细菌的使用的可复制的表达载体。

公开(公告)号：US06623737B2

公开(公告)日：2003-09-23

申请号：US09054141

申请日：1998-04-02

申请人： Gordon Dougan ,  Gad Frankel

发明人： Gordon Dougan ,  Gad Frankel

IPC分类号： A61K39395

CPC分类号： C07K16/1232 ,  C07K14/245 ,  C07K2319/00 ,  Y10S530/825

摘要： The invention is related to antibodies, particularly monoclonal antibodies, which recognize particularly epitopes of the intimin protein of enteropathogenic E. coli and enterohemorrhagic E. coli, methods of detecting such E. coli by use of these antibodies, and kits containing these antibodies for diagnosis.

摘要翻译： 本发明涉及特异性识别肠致病性大肠杆菌和肠出血性大肠杆菌肠粘蛋白表位的抗体，特别是单克隆抗体，使用这些抗体检测这种大肠杆菌的方法，以及含有这些用于诊断的抗体的试剂盒 。

公开(公告)号：US5811105A

公开(公告)日：1998-09-22

申请号：US449297

申请日：1995-05-24

申请人： Gordon Dougan ,  Steven Neville Chatfield ,  Carlos Estenio Hormaeche

发明人： Gordon Dougan ,  Steven Neville Chatfield ,  Carlos Estenio Hormaeche

IPC分类号： A61K39/02 ,  A61K39/112 ,  C12N15/00 ,  C12N1/00

CPC分类号： A61K39/0275 ,  A61K2039/522

摘要： An attenuated microorganism harboring two mutated genes, each of which is located in the organisms aromatic pathway is provided. These organisms can usefully form the basis of a vaccine. They can be genetically engineered so as to express antigens from other pathogens and thus form the basis of a range of multi-valent vaccines.

摘要翻译： 提供了含有两个突变基因的减毒微生物，每个基因位于生物体芳香途径中。 这些生物体可有效地形成疫苗的基础。 它们可以被遗传工程化，以便表达来自其他病原体的抗原，从而形成一系列多价疫苗的基础。