VESICULAR STOMATITIS VIRUS FOR PRIME BOOST VACCINE

    公开(公告)号:US20140370043A1

    公开(公告)日:2014-12-18

    申请号:US14368102

    申请日:2012-12-21

    IPC分类号: C07K14/005 C12N7/00

    摘要: The present invention relates to vesicular stomatitis virus (VSV) matrix (M) protein mutants. One mutant M protein includes a glycine changed to a glutamic acid at position (21), a leucine changed to a phenylalanine at position (111) and a methionine changed to an arginine at position (51). Another M protein mutant includes a glycine changed to a glutamic acid at position (22) and a methionine changed to an arginine at positions (48) and (51). Yet another VSV M protein mutant includes a glycine changed to a glutamic acid at position (22), a leucine changed to a phenylalanine at position (110) and a methionine changed to an arginine at positions (48) and (51). The present invention is directed also to recombinant VSVs (rVSV) having these M mutants and to vaccines based on the rVSV having the M mutants of the present invention. These new rVSVs having the mutant M were significantly attenuated and lost virulence, including neurovirulence, and are capable of inducing an immune responses against an antigen of interest. In addition, a rVSV serotype Indiana having the first described M mutant is capable of efficient replication at 31° C., and of poor replication or incapable of replication at about 37° C. or higher.

    摘要翻译: 本发明涉及水泡性口炎病毒(VSV)基质(M)蛋白质突变体。 一个突变体M蛋白包括在位置(21)改变为谷氨酸的甘氨酸,在位置(111)将亮氨酸改变为苯丙氨酸,在(51)位置变成精氨酸的甲硫氨酸。 另一个M蛋白突变体包括在位置(22)改变为谷氨酸的甘氨酸和位置(48)和(51)处的甲硫氨酸变为精氨酸。 另一种VSV M蛋白突变体包括在位置(22)改变为谷氨酸的甘氨酸,在位置(110)将亮氨酸变为苯丙氨酸,在位置(48)和(51)将甲硫氨酸变为精氨酸。 本发明还涉及具有这些M突变体的重组VSV(rVSV)和基于具有本发明的M突变体的rVSV的疫苗。 具有突变体M的这些新的rVSV显着减毒并丧失毒力,包括神经毒力,并且能够诱导针对感兴趣的抗原的免疫应答。 此外,具有第一个描述的M突变体的rVSV血清型印第安纳能够在31℃下有效复制,并且在约37℃或更高时能够复制性差或不能复制。