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1. 发明授权

US07270821B2 Hepatitis B core antigen fusion proteins 有权
标题翻译：乙型肝炎核心抗原融合蛋白
公开(公告)号：US07270821B2
公开(公告)日：2007-09-18
申请号：US10240917
申请日：2001-04-09
申请人： Annick Gehin , Robert Gilbert , David Stuart , David Rowlands
发明人： Annick Gehin , Robert Gilbert , David Stuart , David Rowlands
IPC分类号： A61K39/00
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K2039/53 , C07K2319/00 , C07K2319/40 , C07K2319/735 , C07K2319/80 , C12N15/62 , C12N2730/10122 , Y02A50/466
摘要： The hepatitis B virus (HBV) capsid is made up of a single species of protein called the core antigen (HBcAg) which self-assembles into particles. The particles are highly immunogenic and are able to present heterologous epitopes to the immune system when the epitopes are inserted into a surface-exposed region of the particles called the “e1 loop”. The structural building blocks of the particles are tightly associated dimers of HBcAg in which the adjacent e1 loops are closely juxtaposed. It is proposed that sequences inserted into the e1 loop are conformationally restrained in the assembled particles when presented in monomeric core protein. The invention seeks to solve this problem by covalently linking core proteins as tandem copies (e.g., as dimers) so that insertions can be made independently in each copy. This is particularly useful for insertion of large sequences into the e1 loop because it allows such sequences to be inserted into just one copy of the core protein per tandem repeat, thereby reducing potential conformational clashes in assembly. Alternatively, a different sequence may be inserted into each e1 loop of a tandem repeat, thus increasing the flexibility of HBcAg particles as an epitope delivery system.
摘要翻译：乙型肝炎病毒（HBV）衣壳由称为核心抗原（HBcAg）的单一种类的蛋白质组成，其自组装成颗粒。当将表位插入称为“e1循环”的颗粒的表面暴露区域中时，颗粒是高度免疫原性的并且能够向免疫系统提供异源表位。颗粒的结构构件是HBcAg的紧密相关的二聚体，其中相邻的e1环相互并置。提出插入到e1环中的序列在单体核心蛋白中呈现时，在组装的颗粒中被构象地约束。本发明寻求通过将核心蛋白质共价连接作为串联拷贝（例如，作为二聚体）来解决这个问题，从而可以在每个拷贝中独立地进行插入。这对于将大序列插入到e1环中是特别有用的，因为它允许这样的序列插入到每个串联重复的核心蛋白的一个拷贝中，从而减少组装中潜在的构象冲突。或者，可以将不同的序列插入到串联重复的每个e1环中，从而增加HBcAg颗粒作为表位递送系统的灵活性。

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