公开(公告)号：EP2802349A4

公开(公告)日：2015-08-26

申请号：EP13736349

申请日：2013-01-10

申请人： STC UNM

发明人： CHACKERIAN BRYCE ,  PEABODY DAVID ,  TUMBAN EBENEZER

IPC分类号： A61K39/12 ,  A61P31/20 ,  C12N7/01

CPC分类号： A61K39/12 ,  A61K2039/5258 ,  A61K2039/58 ,  C12N2710/20034 ,  C12N2795/18142 ,  C12N2795/18143

摘要： In one aspect, the invention provides immunogenic HPV L2-containing viral-like particles (VLPs). Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. In certain aspects, the VLPs are comprised of a coat polypeptide of the bacteriophages PP7 or MS2, wherein the coat protein is modified by insertion of peptide antigens derived from HPV L2, and wherein the HPV L2 peptide is displayed on the VLP and encapsidates PP7 or MS2 mRNA. Specifically, VLPs of the invention display L2 peptides at the N- terminus of the bacteriophage coat protein. Surprisingly, these L2-displaying VLPs induce more broadly neutralizing antibody responses than when the same peptide is displayed in the AB-loop such that the immunogenic response is enhanced by a factor of at least 10. Immunogenic VLPs and related compositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge in vivo.

摘要翻译： 一方面，本发明提供了含免疫原性的含有HPV L2的病毒样颗粒（VLP）。 还提供了相关组合物（例如疫苗），核酸构建体和治疗方法。 在某些方面，VLP由噬菌体PP7或MS2的外壳多肽组成，其中通过插入衍生自HPV L2的肽抗原修饰外壳蛋白，并且其中HPV L2肽显示在VLP上并且包裹PP7或 MS2 mRNA。 具体地，本发明的VLP在噬菌体外壳蛋白的N-末端显示L2肽。 令人惊讶的是，这些L2显示的VLP诱导比在AB环中显示相同的肽更广泛的中和抗体应答，使得免疫原性应答增加至少10倍。本发明的免疫原性VLP和相关组合物诱导高 针对HPV L2的滴度抗体应答和在体内防止HPV挑战。