Plasmid encoding B-cell activating factor receptor (BAFF-R) and uses of same in the treatment and prevention of inflammatory diseases in fish
The present invention relates to a plasmid that encodes a fusion protein comprising a signal peptide and the extracellular domain of the B-cell activating factor receptor (BAFF-R), and optionally, a fragment of the constant region (Fc) of an immunoglobulin. The invention also relates to compositions comprising said plasmid, and to the use of same in the treatment and/or prevention of inflammatory diseases in fish, more preferably in salmonids.
1 . A fusion protein comprising an amino acid sequence comprising at least 95% identity to SEQ ID NO: 10 that comprises a first amino acid sequence comprising an interleukin (IL-2) signal peptide fused to a second amino acid sequence corresponding to an extracellular domain of the BAFF receptor (B-cell activating factor receptor, BAFF-R), wherein the signal peptide directs the extracellular domain of the fusion protein to BAFF, which fusion protein binds to BAFF and inhibits BAFF-mediated signaling.
2 . A composition comprising the fusion protein according to claim 1 , and at least one of: an excipient and a carrier.
3 . The composition according to claim 2 , characterized in that it is a pharmaceutical or veterinary composition.
4 . A fusion protein comprising a first amino acid sequence comprising the interleukin-2 (IL-2) signal peptide of SEQ ID NO: 2 fused to a second amino acid sequence comprising at least 95% identity to the extracellular domain of the BAFF receptor (B-cell activating factor receptor, BAFF-R) of SEQ ID NO: 4; wherein the fusion protein comprises at least 95% identity to SEQ ID NO: 10 and the signal peptide directs the extracellular domain of the fusion protein to BAFF, which fusion protein binds to BAFF and inhibits BAFF-mediated signaling.
5 . A nucleic acid encoding the fusion protein according to claim 1 .
6 . The nucleic acid according to claim 5 , comprising a sequence with at least 95% identity to any of SEQ ID NO: 7 or SEQ ID NO: 9.
7 . A plasmid comprising a nucleic acid molecule according to claim 5 , wherein, at least one of:
a) the nucleic acid molecule is operably bonded to an expression control sequence suitable for expression in a host cell; and
b) the plasmid comprises one or more selectable marker genes.
8 . The plasmid according to claim 7 , characterized in that it comprises SEQ ID NO: 11.
9 . A host cell comprising a nucleic acid molecule according to claim 5 .
10 . A composition comprising the nucleic acid according to claim 5 , and at least one of: an excipient and a carrier.
11 . A method for the treatment, whether prophylactic or therapeutic, of one or more inflammatory diseases in a salmonid animal that comprises the administration of a therapeutically effective amount of the fusion protein according to claim 1 to salmonid animal in need thereof.
12 . The method according to claim 11 wherein the administration is by intramuscular route.
13 . The method of claim 11 , wherein the one or more inflammatory diseases are caused by myxozoans of the genus Tetracapsuloides.
14 . The method according to claim 11 , wherein the one or more inflammatory diseases are Proliferative Kidney Disease and the Red Mark Syndrome.
15 . The method according to claim 11 , wherein the salmonid animal is selected from the list consisting of: Rainbow trout ( Oncorhynchus mykiss ); Chinook salmon ( Oncorhynchus tshawytscha ); Coho salmon ( Oncorhynchus kisutch ); Atlantic salmon ( Salmo salar ); Common trout ( Salmo trutta ); Grayling ( Thymallus thymallus ); Whitefish ( Coregonus spp.); Chum salmon ( Oncorhynchus keta ); Sockeye salmon ( Oncorhynchus nerka ); Lake trout ( Salvelinus namaycush ); Brook trout ( Salvelinus fontinalis ) and Arctic char ( Salvelinus alpinus ).
16 . The method according to claim 11 , wherein the salmonid animal is one of Rainbow trout ( Oncorhynchus mykiss ) and Common trout ( Salmo trutta ).