MODIFIED MATRIX PROTEINS OF VESICULAR STOMATITIS VIRUS

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 alanine 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). These new rVSVs having the mutant M are 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.

主权项

1. A modified matrix (M) protein of a vesicular stomatitis virus (VSV), wherein the modified M protein comprises an amino acid sequence selected from: (i) SEQ ID NO: 3 including at least the following substitutions: G21E/L111A/M51R; and (ii) SEQ ID NO: 8 including at least the following substitutions: G22E/L110A/M48R/M51R.