Recombinant novirhabdovirus usable as an antigen vector
View Patent ↗The invention relates to a recombinant novirhabdovirus expressing a chimeric protein comprising the sequence of an antigen of interest flanked, at the N-terminus, by a signal peptide, and at the C-terminus, by a polypeptide comprising at least one portion of the transmembrane domain of a rhabdovirus G protein. Said recombinant novirhabdovirus can be used especially for inducing an immune response to the antigen of interest.
1. A recombinant novirhabdovirus, the genome of which comprises the genes encoding the endogenous N, P, M, G and L proteins of said novirhabdovirus, and an exogenous gene encoding a chimeric protein, wherein said chimeric protein comprises the sequence of an antigenic protein of interest fused, at its N-terminal end, with a novirhabdovirus G protein signal peptide and, at its C-terminal end, with a novirhabdovirus G protein sequence fragment, said fragment comprising the transmembrane domain of said novirhabdovirus G protein or a portion thereof, said portion of the transmembrane domain comprises at least 15 consecutive C-terminal amino acids of said domain and wherein said antigenic protein of interest is not a glycoprotein.
2. The recombinant novirhabdovirus as claimed in claim 1 , further comprising, the intravirion domain of a novirhabdovirus G protein, or a portion of said intravirion domain, said intravirion domain or said portion thereof being C-terminal to the transmembrane domain or the portion thereof, and said intravirion domain or the portion thereof following said transmembrane domain or the portion thereof.
3. The recombinant novirhabdovirus as claimed in claim 2 , wherein said portion of the intravirion domain comprises at least three consecutive N-terminal amino acids of said domain.
4. The recombinant novirhabdovirus as claimed in claim 1 , wherein said recombinant novirhabdovirus is devoid of the endogenous NV gene, and in that the gene encoding the chimeric protein is inserted as a replacement for said NV gene.
5. The recombinant novirhabdovirus as claimed in claim 1 , wherein said recombinant novirhabdovirus contains the endogenous NV gene, and in that the gene encoding the chimeric protein is inserted into an additional transcription unit placed in an intergenic region of the viral genome.
6. The recombinant novirhabdovirus as claimed in claim 5 , further comprising at least two additional transcription units, each of which comprising an exogenous gene encoding-said chimeric protein.
7. The recombinant novirhabdovirus as claimed in claim 1 , wherein the recombinant novirhabdovirus is chosen from an infectious hematopoietic necrosis virus and a viral hemorrhagic septicaemia virus.
8. An isolated cDNA encoding the genome of a recombinant novirhabdovirus as claimed in claim 1 .
9. A method of inducing an immune response in a subject, comprising administering to the subject a vaccine comprising the recombinant novirhabdovirus of claim 1 , wherein the immune response is directed against the antigen of interest expressed by said novirhabdovirus.
10. The method of claim 9 wherein said vaccine is selected the group consisting of an antiviral vaccine, an antibacterial vaccine, an antifungal vaccine, an antiparasitic vaccine and an antitumor vaccine.
11. A method of producing antibodies in a subject, comprising administering to the subject the recombinant novirhabdovirus of claim 1 , wherein the antibodies are directed against the antigen of interest expressed by said novirhabdovirus.