Modified Sendai virus vaccine and imaging vector
The present invention relates to a Sendai virus or recombinant Sendai virus vector. In particular the present invention provides methods, vectors, formulations, compositions, and kits for a modified Enders strain Sendai viral vector. An immunogenic vector can be used in any in vitro or in vivo system. Moreover, some embodiments include vectors for imaging virus growth, location and transmission.
1. An immunogenic recombinant mutant Enders Sendai viral vector comprising
a) a modified Enders Sendai virus L gene that encodes a modified L protein containing one or more amino acid mutations of the wild type L protein selected from the group consisting of wild type amino acid S to mutant amino acid G at position 155, wild type amino acid R to mutant amino acid K at position 258, wild type amino acid G to mutant amino acid E at position 466, wild type amino acid G to mutant amino acid E at position 482, wild type amino acid S to mutant amino acid R at position 581, wild type amino acid Q to mutant amino acid R at position 717, wild type amino acid T to mutant amino acid I at position 800, and wild type amino acid R to mutant amino acid K at position 852, and
b) one or more heterologous genes that comprise a gene encoding an antigen.
2. The recombinant Sendai viral vector of claim 1 , wherein said one or more heterologous genes are inserted in one or more intergenic junction selected from the group consisting of N-P junction, P-M junction, M-F junction, F-HN junction, and HN-L junction.
3. The recombinant Sendai viral vector of claim 2 , wherein said one or more heterologous genes further comprises a gene that facilitate virus tracking in vitro, in vivo, or both.
4. The recombinant Sendai viral vector of claim 3 , wherein said gene that facilitates virus tracking is selected from the group consisting of luciferase, green fluorescent protein, and both luciferase and green fluorescent protein.
5. The recombinant Sendai viral vector of claim 1 , further comprising at least one of mutant gene start sequence and of mutant gene stop sequence to alter gene transcription.
6. The recombinant Sendai viral vector of claim 1 , wherein said heterologous gene encoding an antigen is selected from the group consisting of respiratory syncytial virus (RSV) F protein, respiratory syncytial virus (RSV) G protein, parainfluenza virus type 1 (PIV-1) protein, parainfluenza virus type 2 (PIV-2) protein, parainfluenza virus type 3 (PIV-3) protein, and parainfluenza virus type 4 (PIV-4) protein.
7. The recombinant Sendai viral vector of claim 3 , wherein said gene that facilitates virus tracking is a reporter gene.
8. A method of immunizing an animal comprising administering to the animal an effective amount of the recombinant Sendai viral vector of claim 1 .
9. The recombinant Sendai viral vector of claim 2 , wherein said one or more heterologous genes are inserted between a Sendai virus P gene and a Sendai virus M gene.
10. The recombinant Sendai viral vector of claim 2 , wherein said one or more heterologous genes are inserted between a Sendai virus M gene and a Sendai virus F gene.
11. The recombinant Sendai viral vector of claim 2 , wherein said one or more heterologous genes are inserted between a Sendai virus F gene and a Sendai virus HN gene.
12. The recombinant Sendai viral vector of claim 1 , wherein said vector further comprises at least one antigen or immunogen.
13. The recombinant Sendai viral vector of claim 5 , wherein said mutant start sequence comprises AGGGTGAAAG (SEQ ID NO: 20).
14. The recombinant Sendai viral vector of claim 1 , wherein said modified L protein comprises SEQ ID NO:17.
15. The recombinant Sendai viral vector of claim 6 , wherein said one or more heterologous gene encoding an antigen comprise RSV F protein, and said vector comprises SEQ ID NO:18.