Attenuated recombinant rabies virus mutants and live vaccines thereof
The present invention describes recombinant RV mutants comprising a combine mutation in two different parts of the viral genome, involving the P and the G genes. The mutations in the P gene preferably encompass residues 139 to 170, more preferably residue 139 to 149, most preferably residues 143-149. The mutation can be a substitution or deletion of one or more amino acids in the above region, as well as combinations of deletion and substitution.
1. A recombinant rabies virus mutant comprising a mutation in the G protein and a mutation in the P protein, which mutation in the P protein is a deletion comprising the amino acids at positions 143 to 149.
2. A mutant according to claim 1 wherein the mutation in the P protein is a deletion selected from the group consisting of amino acids 143 to 149 and 139 to 149.
3. A mutant according to claim 1 wherein the mutation in the P protein is a deletion of amino acids 139 to 149.
4. A mutant according to claim 1 wherein the mutation in the G protein is an amino acid substitution of the arginine at position 333 for another amino acid.
5. A mutant according to claim 4 wherein the Arg 333 is replaced with Asp.
6. A mutant according to claim 4 , wherein the Arg 333 codon is replaced with GAC.
7. A mutant according to claim 1 wherein the mutation in the G protein is a replacement of the Arg 333 codon with GAC and wherein the mutation in the P protein is a deletion of amino acids 139 to 149.
8. A mutant according to claim 1 where said mutant is a mutant of RV strain SAD Bern or SAD B19.
9. A recombinant rabies virus according to claim 1 additionally expressing a nucleic acid encoding a heterologous antigen.
10. A recombinant rabies virus according to claim 9 wherein the said antigen derived from human or animal pathogen.
11. A recombinant rabies virus according to claim 9 additionally expressing a gene encoding an immune-stimulatory protein.
12. A vaccine comprising a mutant according to claim 1 .
13. The vaccine of claim 12 wherein the—mutant comprises a mutation in the G protein wherein the—Arg 333 codon is replaced with GAC and wherein the mutation in the P protein is a deletion of amino acids 139-149.
14. The vaccine of claim 12 wherein the mutation comprises a mutation in the P protein which encompasses one or more of the amino acids at positions 143 to 149 and 139 to 149.
15. The vaccine of claim 12 wherein the—mutant comprises a—mutation in the G protein—wherein—the arginine at position 333—is substituted—for another amino acid.
16. The vaccine of claim 12 wherein the—mutant comprises a mutation in the G protein wherein the—Arg 333 codon is replaced with GAC or the Arg 333 codon is replaced with Asp.
17. The vaccine of claim 12 wherein said mutant is a mutant selected from the group consisting of RV strain SAD Bern and SAD B19.
18. A recombinant rabies virus mutant comprising a mutation in the G protein and a mutation one or more of the amino acids at positions 143 to 149 and 139 to 149 in the P protein.