公开(公告)号：US20040209241A1

公开(公告)日：2004-10-21

申请号：US10738986

申请日：2003-12-19

申请人： Vical Incorporated

发明人： Gary G. Hermanson ,  Andrew J. Geall ,  Mary Kopke Wloch

IPC分类号： C07K014/02 ,  C12Q001/70 ,  C07H021/04

CPC分类号： A61K38/16 ,  A61K35/763 ,  A61K38/162 ,  A61K39/00 ,  A61K39/12 ,  A61K39/245 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55555 ,  A61K2039/55572 ,  C07H21/00 ,  C07K14/005 ,  C07K14/045 ,  C12N2710/16122 ,  C12N2710/16134 ,  C12N2800/22

摘要： The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

摘要翻译： 本发明涉及基于多核苷酸的巨细胞病毒疫苗。 特别地，本发明是可操作地编码HCMV抗原的质粒，其中用于HCMV抗原的天然存在的编码区已通过密码子优化被修饰以改善人或其他哺乳动物细胞中的翻译。 可用于本发明的HCMV抗原包括但不限于pp65，糖蛋白B（gB），IE1以及这些抗原之一的片段，变体或衍生物。 在某些实施方案中，已经删除了序列，例如pp65中的Arg435-Lys438推定的激酶和gB中的膜锚定和内细胞域。 本发明还涉及在哺乳动物例如人中诱导对HCMV的免疫应答的方法，其包括如上所述递送编码密码子优化的HCMV抗原的质粒。 本发明还涉及包含编码如上所述的密码子优化的HCMV抗原的质粒的药物组合物，并且还包含佐剂，赋形剂或免疫调节剂。