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公开(公告)号：US08637234B2
公开(公告)日：2014-01-28
申请号：US11578761
申请日：2005-04-08
申请人： George M. Shaw , James E. Robinson , Frederic Bibollet-Ruche , Julie M. Decker , Beatrice H. Hahn , Peter D. Kwong
发明人： George M. Shaw , James E. Robinson , Frederic Bibollet-Ruche , Julie M. Decker , Beatrice H. Hahn , Peter D. Kwong
CPC分类号： G01N33/56988 , C07K16/1063 , C07K16/2812 , C07K2317/32 , C07K2317/34 , C07K2317/76 , G01N2469/20
摘要： Methods and compositions are provided for the use of an envelope polypeptide or a functional variant thereof from a lentivirus that is not HIV-1 as a molecular scaffold for HIV-1 epitopes. The HIV-1 epitopes can be recognized by HIV-1 binding antibodies, HIV-1 neutralizing antibodies and/or CD4-induced antibodies. Thus, methods are provided for detecting HIV-1 binding antibodies in a subject infected with HTV-1. Further provided are methods to determine an epitope for an HIV-1 binding antibody; methods to assay for an HIV-1 binding antibody; methods to identify a soluble CD4 mimic; methods to neutralize an non-HIV-1 virus; diagnostic assays to monitor HIV disease in a subject or to monitor the subject's response to immunization by a HIV vaccine; and methods to alter the neutralization potential of an HIV-1 derived CD4-induced antibody. Chimeric polypeptides, chimeric polynucleotides, kits, cells and viruses are also provided.
摘要翻译： 提供了使用来自不是HIV-1作为HIV-1表位的分子支架的慢病毒的包膜多肽或其功能变体的方法和组合物。 HIV-1表位可被HIV-1结合抗体，HIV-1中和抗体和/或CD4诱导的抗体识别。 因此，提供了用于检测感染HTV-1的受试者中的HIV-1结合抗体的方法。 还提供了确定HIV-1结合抗体的表位的方法; 测定HIV-1结合抗体的方法; 识别可溶性CD4模拟物的方法; 中和非HIV-1病毒的方法; 用于监测受试者中艾滋病病毒的诊断测定或监测受试者对HIV疫苗免疫接种的反应; 以及改变HIV-1衍生的CD4诱导抗体的中和电位的方法。 还提供嵌合多肽，嵌合多核苷酸，试剂盒，细胞和病毒。
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公开(公告)号：US08647818B2
公开(公告)日：2014-02-11
申请号：US11816624
申请日：2006-02-16
CPC分类号： A61K39/21 , A61K39/12 , A61K39/385 , A61K2039/53 , A61K2039/6075 , A61K2039/64 , C07K14/005 , C07K2319/00 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134
摘要： Methods and compositions are provided which employ chimeric polypeptides having at least one heterologous epitope for a human immunodeficiency virus type 1 (HIV-1) neutralizing antibody. These chimeric polypeptides behave as molecular scaffolds which are capable of presenting the various heterologous HIV-1 epitopes. The invention demonstrates that a heterologous epitope recognized by the HIV-1 neutralizing antibody can be more fully exposed to neutralizing antibodies when presented within the backbone of the chimeric polypeptide than when the epitope is presented within the context of an HIV-1 backbone. Polynucleotides encoding these chimeric polypeptides are also provided. Immunogenic compositions are provided which comprise a chimeric polypeptide having at least one heterologous epitope that interacts with an HIV-1 neutralizing antibody. Immuno genie compositions comprising chimeric polynucleotides encoding the chimeric polypeptides of the invention are also provided. Vaccines comprising such immunogenic compositions are also provided. Further provided are methods which employ the immunogenic compositions of the invention. Such methods include, for example, methods for eliciting an immune response in a subject, methods for generating antibodies specific for the chimeric polypeptide or the chimeric polypeptide, and methods for inhibiting or preventing infection by HIV-1 in a subject.
摘要翻译： 提供了使用针对人免疫缺陷病毒1型（HIV-1）中和抗体具有至少一个异源表位的嵌合多肽的方法和组合物。 这些嵌合多肽表现为能够呈递各种异源HIV-1表位的分子支架。 本发明证明当HIV-1中和抗体在HIV-1主链的上下文中呈现时，HIV-1中和抗体识别的异源表位可以更好地暴露于中和抗体。 还提供了编码这些嵌合多肽的多核苷酸。 提供免疫原性组合物，其包含具有至少一种与HIV-1中和抗体相互作用的异源表位的嵌合多肽。 还提供了包含编码本发明的嵌合多肽的嵌合多核苷酸的免疫精华组合物。 还提供了包含这种免疫原性组合物的疫苗。 还提供了采用本发明的免疫原性组合物的方法。 这样的方法包括例如在受试者中引发免疫应答的方法，用于产生对嵌合多肽或嵌合多肽具有特异性的抗体的方法，以及用于抑制或预防受试者中HIV-1感染的方法。
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公开(公告)号：US20090162390A1
公开(公告)日：2009-06-25
申请号：US11816624
申请日：2006-02-16
IPC分类号： A61K39/21 , A61K31/711 , C07K14/155 , C12N15/31 , A61P31/18
CPC分类号： A61K39/21 , A61K39/12 , A61K39/385 , A61K2039/53 , A61K2039/6075 , A61K2039/64 , C07K14/005 , C07K2319/00 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134
摘要： Methods and compositions are provided which employ chimeric polypeptides having at least one heterologous epitope for a human immunodeficiency virus type 1 (HIV-1) neutralizing antibody. These chimeric polypeptides behave as molecular scaffolds which are capable of presenting the various heterologous HIV-1 epitopes. The invention demonstrates that a heterologous epitope recognized by the HIV-1 neutralizing antibody can be more fully exposed to neutralizing antibodies when presented within the backbone of the chimeric polypeptide than when the epitope is presented within the context of an HIV-1 backbone. Polynucleotides encoding these chimeric polypeptides are also provided. Immunogenic compositions are provided which comprise a chimeric polypeptide having at least one heterologous epitope that interacts with an HIV-1 neutralizing antibody. Immuno genie compositions comprising chimeric polynucleotides encoding the chimeric polypeptides of the invention are also provided. Vaccines comprising such immunogenic compositions are also provided. Further provided are methods which employ the immunogenic compositions of the invention. Such methods include, for example, methods for eliciting an immune response in a subject, methods for generating antibodies specific for the chimeric polypeptide or the chimeric polypeptide, and methods for inhibiting or preventing infection by HIV-1 in a subject.
摘要翻译： 提供了使用针对人免疫缺陷病毒1型（HIV-1）中和抗体具有至少一个异源表位的嵌合多肽的方法和组合物。 这些嵌合多肽表现为能够呈递各种异源HIV-1表位的分子支架。 本发明证明当HIV-1中和抗体在HIV-1主链的上下文中呈现时，HIV-1中和抗体识别的异源表位可以更好地暴露于中和抗体。 还提供了编码这些嵌合多肽的多核苷酸。 提供免疫原性组合物，其包含具有至少一种与HIV-1中和抗体相互作用的异源表位的嵌合多肽。 还提供了包含编码本发明的嵌合多肽的嵌合多核苷酸的免疫精华组合物。 还提供了包含这种免疫原性组合物的疫苗。 还提供了采用本发明的免疫原性组合物的方法。 这样的方法包括例如在受试者中引发免疫应答的方法，用于产生对嵌合多肽或嵌合多肽具有特异性的抗体的方法，以及用于抑制或预防受试者中HIV-1感染的方法。
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公开(公告)号：US20080096187A1
公开(公告)日：2008-04-24
申请号：US11578761
申请日：2005-04-08
CPC分类号： G01N33/56988 , C07K16/1063 , C07K16/2812 , C07K2317/32 , C07K2317/34 , C07K2317/76 , G01N2469/20
摘要： Methods and compositions are provided for the use of an envelope polypeptide or a functional variant thereof from a lentivirus that is not HIV-1 as a molecular scaffold for HIV-1 epitopes. The HIV-1 epitopes can be recognized by HIV-1 binding antibodies, HIV-1 neutralizing antibodies and/or CD4-induced antibodies. Thus, methods are provided for detecting HIV-1 binding antibodies in a subject infected with HTV-1. Further provided are methods to determine an epitope for an HIV-1 binding antibody; methods to assay for an HIV-1 binding antibody; methods to identify a soluble CD4 mimic; methods to neutralize an non-HIV-1 virus; diagnostic assays to monitor HIV disease in a subject or to monitor the subject's response to immunization by a HIV vaccine; and methods to alter the neutralization potential of an HIV-1 derived CD4-induced antibody. Chimeric polypeptides, chimeric polynucleotides, kits, cells and viruses are also provided.
摘要翻译： 提供了使用来自不是HIV-1作为HIV-1表位的分子支架的慢病毒的包膜多肽或其功能变体的方法和组合物。 HIV-1表位可被HIV-1结合抗体，HIV-1中和抗体和/或CD4诱导的抗体识别。 因此，提供了用于检测感染HTV-1的受试者中的HIV-1结合抗体的方法。 还提供了确定HIV-1结合抗体的表位的方法; 测定HIV-1结合抗体的方法; 识别可溶性CD4模拟物的方法; 中和非HIV-1病毒的方法; 用于监测受试者中艾滋病病毒的诊断测定或监测受试者对HIV疫苗免疫接种的反应; 以及改变HIV-1衍生的CD4诱导抗体的中和电位的方法。 还提供了嵌合多肽，嵌合多核苷酸，试剂盒，细胞和病毒。
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