公开(公告)号：EP3079718A1

公开(公告)日：2016-10-19

申请号：EP14870178.2

申请日：2014-12-11

申请人： The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

发明人： CUI, Xinle ,  SNAPPER, Clifford M. ,  MOND, James J.

IPC分类号： A61K39/245 ,  C07K14/03 ,  C07K14/045

CPC分类号： A61K39/245 ,  A61K39/00 ,  A61K39/12 ,  A61K2039/575 ,  A61K2039/70 ,  C07K7/08 ,  C07K14/005 ,  C07K2319/02 ,  C07K2319/21 ,  C12N7/00 ,  C12N2710/16122 ,  C12N2710/16134 ,  C12N2710/16222 ,  C12N2710/16234

摘要： The present disclosure provides modified human herpesvirus glycoprotein B (gB) proteins that incorporate unique mechanisms for generating proteins that mimic their native conformation to enhance their immunogenicity. The modified herpesvirus gB proteins insert a peptide linker at the furin cleavage site in the extracellular domain of herpesvirus gB. When expressed, the gB subunit associates in triplicate to produce a homotrimeric complex, mimicking the native conformation of the gB protein. Also provided are protein complexes comprising a homotrimeric complex of a modified herpesvirus gB protein and herpesvirus gH and gL proteins. Also provided are nucleic acids encoding the modified herpesvirus gB proteins, methods of inducing or suppressing an immune response in a subject by administering a vaccine comprising the modified herpesvirus gB protein, or nucleic acid encoding the same, or a protein complex comprising a homotrimeric complex of the modified herpesvirus gB protein and herpesvirus gH and gL proteins.

摘要翻译： 本公开提供修饰的人疱疹病毒糖蛋白B（gB）蛋白，其掺入产生模拟其天然构象以增强其免疫原性的蛋白质的独特机制。 修饰的疱疹病毒gB蛋白在疱疹病毒gB的细胞外结构域的弗林蛋白酶切割位点插入肽接头。 当表达时，gB亚基一式三份结合以产生同源三聚体，模拟gB蛋白的天然构象。 还提供了包含修饰的疱疹病毒gB蛋白和疱疹病毒gH和gL蛋白的同三聚体复合物的蛋白质复合物。 还提供了编码修饰的疱疹病毒gB蛋白的核酸，通过施用包含修饰的疱疹病毒gB蛋白的疫苗或编码该疱疹病毒gB蛋白的核酸或包含同源三聚体复合物的蛋白质复合物的蛋白质复合物来诱导或抑制受试者的免疫应答的方法 修饰的疱疹病毒gB蛋白和疱疹病毒gH和gL蛋白。

公开(公告)号：EP2877205A2

公开(公告)日：2015-06-03

申请号：EP13823370.5

申请日：2013-07-26

申请人： The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

发明人： MOND, James, J. ,  SNAPPER, Clifford, M ,  CUI, Xinle

IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K39/385 ,  A61K39/02

CPC分类号： A61K39/245 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/53 ,  A61K2039/55505 ,  A61K2039/55561 ,  A61K2039/57 ,  A61K2039/70 ,  C07K14/005 ,  C07K2319/00 ,  C12N2710/16234 ,  C12N2740/15022 ,  C12N2740/15034 ,  Y02A50/386 ,  Y02A50/403 ,  Y02A50/478

摘要： The present disclosure provides fusion proteins that incorporate unique mechanisms for multimerizmg antigens to enhance their immunogenicity. The fusion proteins comprise at least two antigens, or other vaccine related proteins, separated by a linker sequence and an oligomerization domain. When expressed, the fusion protein forms a muKimeric protein complex, This approach can be used to muHimeri?.e a single antigen/protein or to create multimers comprising two or more different antigens/proteins. Also provided are nucleic acids encoding the fusion proteins, Yet another aspect is directed to methods of inducing or suppressing an immune response in a subject by administering to the subject a vaccine composition comprising a fusion protein or nucleic acid encoding the fusion protein, optionally without using an adjuvant.