Vaccines against tenacibaculum finnmarkense

Abstract

A vaccine comprising a Tenacibaculum antigen and methods of using said vaccine to protect salmonids against clinical signs of Tenacibaculum infection are provided.

Description

Vaccines Against Tenacibaculum finnmarkenseFIELD OF THE INVENTION

[0001] This invention is generally in the field of aquaculture vaccines.BACKGROUND

[0002] Ulcerous skin conditions are among the most important causes of economic loss and poor welfare in sea-farmed Atlantic salmon (Salmo salar) in Norway. While bacteriological investigation of lesions and internal organs may result in culture of a variety of different bacterial species, Moritella viscosa, Aliivibrio wodanis and various Tenacibaculum spp. have been most commonly associated with these conditions in Norwegian salmon farming.

[0003] The characteristic signs of tenacibaculosis are ulcerative lesions on the head, fin and skin of the fish, often referred to skin and mouth rot, including hemorrhages and degradation of the tissues, which end up causing death of the fish or the deterioration of their welfare and external appearance, making the affected fish unmarketable.

[0004] Tenacibaculum finnmarkense is a Gram-stain negative, aerobic, non-flagellated, rodshaped gliding bacterial strain that belongs to the genus Tenacibaculum. It was first isolated in 2014 from a skin lesion of a diseased Atlantic salmon (Salmo salar} in Finnmark, Norway. See, e.g., CA2951765 or EP3155088.

[0005] The treatment of tenacibaculosis is carried out through the administration of antimicrobials, generally in combination with external disinfectants. However, the use of antimicrobials to control diseases in fish is limited by increasingly higher restrictions on the use of antibiotics in aquaculture, as well as the rapid acquisition of drug resistance observed in these bacteria. The most promising alternative to the use of antimicrobials is prevention of disease through the use of effective vaccines.

[0006] While vaccines against some bacteria causing ulcers, e.g., M viscosa, are commercially available (e.g., ALPHA JECT® Moritella), there is still no vaccine against T finnmarkense.SUMMARY OF THE INVENTION

[0007] In the first aspect, disclosed herein are vaccines comprising a Tenacibaculum antigen selected from the group consisting of a) an isolated SEQ ID NO: 1 or an amino acid sequence that is at least 90% identical to SEQ ID NO: 1; or b)an isolated SEQ ID NO: 2 or an amino acid sequence that is at least 90% identical to SEQ ID NO: 2; or c) a combination of 'a' and 'b'; wherein said vaccine is a W / O emulsion and wherein said Tenacibaculum antigen is present in the amount of at least 30 micrograms per dose. Also disclosed herein is the vaccine described above, wherein the Tenacibaculum antigen is present in the amount of at least 50 micrograms per dose.

[0008] In certain embodiments, in the vaccines described herein the Tenacibaculum antigen is SEQ ID NO: 1 or 2 or an amino acid sequence that is at least 95% identical thereto. Preferably, the Tenacibaculum antigen is a conservatively substituted variant of SEQ ID NO: 1 or 2. Most preferably, the Tenacibaculum antigen SEQ ID NO: 1.

[0009] In an additional subset of embodiments, the vaccines described in the previous paragraph further comprise one or more additional antigens selected from the group consisting of IPNV, ISAV, SPDV, Aeromonas salmonicida, Vibrio anguillarum 01, 02, Vibrio (Aliivibrio) salmonicida, Yersinia ruckeri 01, Moritella viscosa, Renibacterium salmoninarum, and Pasteurella atlantica.

[0010] In an alternative subset of embodiments, the one or more additional antigens are selected form the group consisting of IPNV, Aeromonas salmonicida, Vibrio anguillarum serotype 1 and 02, and Vibrio (Aliivibrio) salmonicida, Renibacterium salmoninorum, and Piscirickettsia sal mon is.

[0011] In the second aspect, the instant disclosure provides the use of the vaccines according to any one of the embodiments of the first aspect in protection of salmonids against Tenacibaculum finnmarkense infection. In certain embodiments, the weight of said salmonid is 20-120 grams. In an additional or an alternative subset of embodiments of this second aspect, disclosed is the use of the vaccine in the salmonid, wherein said salmonid is Atlantic salmon (Salmo salor). Alternatively, the salmonid is coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), sockeye salmon (Oncorhynchus nerka), Chinook salmon (Oncorhynchus tshawytscha).DETAILED DESCRIPTION

[0012] For a better understanding of the invention, the following definitions will be provided:

[0013] The term "about" or "approximately," when used in connection with a measurable numerical variable, refers to the indicated value of the variable and to all values of the variable that are within the experimental error of the indicated value (e.g., within the 95% confidence interval for the mean) or within 10 percent of the indicated value, whichever is greater.

[0014] The term "pharmaceutically acceptable" refers to substances, which are within the scope of sound medical judgment, suitable for use in contact with the tissues of subjects without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit-to- risk ratio, and effective for their intended use.

[0015] The term "protecting" refers to preventing an infection, disorder, condition, or disease to which such term applies, or to preventing or reducing frequency, intensity or duration of one or more symptoms of such infection, disorder, condition, or disease. Thus, protection from Tenacibaculum finnmarkense infection encompasses reduction of frequency, duration or intensity of at least one clinical sign of Tenacibaculum finnmarkense infection. In preferred embodiments, the at least one clinical sign is mortality.

[0016] The term "subject" refers to fish for which the administration of an adjuvant composition is desired.

[0017] The phrase "therapeutically effective amount" refers to an amount of an antigen or vaccine that would induce an immune response in a subject receiving the antigen or vaccine which is adequate to prevent or reduce signs or symptoms of disease, including adverse health effects or complications thereof, caused by infection with a pathogen, such as a virus or a bacterium. Humoral immunity or cell-mediated immunity or both humoral and cell-mediated immunity may be induced. The immunogenic response to a vaccine may be evaluated indirectly through measurement of antibody titers, lymphocyte proliferation assays, or directly through monitoring signs and symptoms after challenge with wild type strain. The protective immunity conferred by a vaccine can also be evaluated by measuring reduction in clinical signs such as mortality, morbidity, overall physical condition, and overall health and performance of the subject.

[0018] The term "vaccine" refers to a composition that elicits protective immunity in the subject.Antigens

[0019] The vaccines described herein comprise a Tenacibaculum antigen selected from : a) an isolated SEQ I D NO: 1(QQAAPALPTSKVKETVACTKGYNHKGHSKHTSSNKMSRANSPDTFAGWASYSGANLVAKLKETTDYD TNLRPLFDYGQYGGSLFSSTNIKAVADAVYNMSASYDGSESSGMLGLVTYLHCASYHEFFQTEVTLNTNAKSAYKLAVKYLSTNARLWDTTEYGLGVLDEFLIMCDYDGLRDKDFVLNVIKTAIRNLTEKDNWRAVVSDQ QM LTKYITAYNRIFFLMFRGMQPVDVAYEASLNNDPEFLQLLSNLATDKELRTENEDLALMVNNAIGEM TRTADSSDVLKDQTEPFIAEIAQSYDRLTPNWYKSIKSINESGNCAKYNLCVNMDDITAEVEAM LFPNTFT FDDGRLKVRTPLDYKTVQELYYASKQVQTQFFRALATDEPVAGDPNLNLNMVVYGTMKNYHDWQTIL NGLATNNGGMYIERGATFYTYQRTFTESTFSLEELFRHEYVHYLQGRYIANGFWGSTDFYKDGRLIWFEE GMAEHFAGSTDNDGVRIRESQGSNVKNEGASEYMTVNEVLNASYAGGFKFYRYGNMLWSYWFKNDI NTARKLINLVRADDVAGFDTEINRLESDYTLQANYLNYLNNVVIDDNNWWEVVTPWEVDDFFVVGNIA DIETEFEAITSKDVSVTLDASTSIRRFKVTGSLNSGQFETELNDLMTQLKSSPTVNNFDYIGGYYKEVSGSN ATFVITGSLRDATVSDAPIADFTSDLPSTIVGGTIQFTNESTGYINSYTWSFPGGTPSTSTEKNPMVVYDTA GTHSVTLTVTSAKSGNNTRTKNNFIKVHDKSTTTYCDTSQGGTGTGIIRVNFSTLDNTSAPQNPANYSDY TSYAAEVKRNKTYPITIEAANTAWPNNVVKVWIDWNQNGDFTDVGEAVFSYEKISETGNITIPSDAALGI TRM RVRYGYGDGKILEPCGYDDYFGEVEDYSINVGIAAATITWAGTTSTDFAEATNWDTNTIPTSYDDVIIPAGLTNYPVISTATEVKTLTIASGATLIANAPLTGTVTYTRNLPTDNWYLVASPLKYETIEQLKKNNTFASGT GTNIGLAPYKNNGTAWNYLTSTSKGNITSGQGYSVKLKNAANLVFTGSINSTAVNYGITKGANDFNLIGN PYTSYVKLGDFFKDNATGTVLSEATIWLWNQNTNSYDLKLGAADANYQIAPGQGFFVSANANTQVTFSKENQSHQSATFQRQAKTQINLSVRENQNNTVKSTKLYYLNGVTTGFDNGYDGSVFGGTTTNYALYSQLV SNTNGKNYAVQSLPINDLENTIVPIGLKAKAGKKIVFSAESMNLPENVSIYLEDKQNNTFTNLSKENYTVTL TTDASQVGQFYLHTSSKELDASIQTPASFSELTVYKSS) or an amino acid sequence that is at least 90% identical to SEQ ID NO: 1; or b) an isolated SEQ I D NO: 2(FFNATIKHLGEHAHSSKNLGAVNGLAEKLTATLATGNADTRYSGTKSIITRLVGNSYVLRDNTRGGGVNTYNSGAQPSYPTTDFTDSDNNWTAAEFNNSAKDNAALDAHWGAEMTYDYFQDKHNRNSYNGSGATIN SYVHYDDVAGGTGYDNAFWNGSVMTYGDGSSNGNEGNGYFDALTSIDVAAHEIGHAVCSNTANLAY QRESGAMNEGFSDIWGAAVEHFAKGNGNDLAPDASVWLIGDEIDRRNGSSALRSMSNPNERNQPDTY GGVNWKEPNCGTPTRSNDYCGVHTNSGVLNYWFYLLTVGGSGTNDINNAFNVDAIGMEKSAKISYRLE ANYLSANSTFEDARVGSITAAEDLYGANSIEVQSVTNAWHAVGVGQAYVEDCTLVAPSNFNATNINDN GFTVTWSAVSEAVSYTVTINEITSVVTDTSKVITGLVSGTIYNCSVAANCVSGEGGTITSKLITTTGEIPLNYCVSKANNVADEYIQKWLGTIDNTSTASNGYSDYTSISTSLIKGESNTITITPKWNGTVYSEGYGVWIDYNKD GDFDDAGETVFTKAKSKTTPINGTFTIPESALNGATRMRVVLKYNATPTACETNIQYGEVEDYTVVIGEG NADTTAPTVPANLAVSNVDKTSVTLNWSAATDNVAVTGYNVYQGATKLGTTTNISTDITSLSPATSYTFS VKAIDAVANESEASNVINVTTLANQLVYCESKGTNSSYEWIDAVSLGGMANTSASNGGYADFTSKIATLG QGSSNEITVSAGFKSTAYTEHWAVWIDFNQNGIFDTSEKWTGASSSKDYLTSTFEVPASALLGQTRMRV SMKYNASQTACETFKDGEVEDYTVNITATTTKEALLSGNRLVNEPSTALQ) or an amino acid sequence that is at least 90% identical to SEQ I D NO: 2; or c) a combination of 'a' and 'b'.

[0020] Thus, in some embodiments, said Tenacibaculum antigen comprises an amino acid sequence that at least 90%, or at least 91%, or at least 92%, or at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%, or 100% identical to SEQ I D NO: 1. I n other embodiments, said Tenacibaculum antigen comprises an amino acid sequence that at least 90%, or at least 91%, or at least 92%, or at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%, or 100% identical to SEQ I D NO: 2.

[0021] Preferably, the mutations leading to the differences from SEQ ID NO: 1 or 2 are substitutions. The skilled person will further acknowledge that alterations of amino acid sequence of the protein it codes may have little, if any, effect on the resulting three-dimensional structure of the protein. For example, a codon for the amino acid alanine, a hydrophobic amino acid, may be substituted by a codon encoding another less hydrophobic residue, such as glycine, or a more hydrophobic residue, such as valine, leucine, or isoleucine. Similarly, changes which result in the substitution of one negatively charged residue for another, such as aspartic acid for glutamic acid, or one positively charged residue for another, such as lysine for arginine, can also be expected to produce a protein with substantially the same functional activity.

[0022] The following six groups each contain amino acids that are typical conservative substitutions for one another: [1] Alanine (A), Serine (S), Threonine (T); [2] Aspartic acid (D), Glutamic acid (E); [3] Asparagine (N), Glutamine (Q); [4] Arginine (R), Lysine (K), Histidine (H); [5] Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and [6] Phenylalanine (F), Tyrosine (Y), Tryptophan (W), (see, e.g., US Patent Publication 20100291549).

[0023] In certain advantageous embodiments, at least half (or at least 60% or at least 70% or at least 80%, or at least 90%, or at least 95% or 100%) of amino acids differing from the corresponding amino acids in the respective reference sequences are conservative substitutions.Dosing

[0024] It is preferred that the total amount of the Tenacibaculum antigen should be at least 30 micrograms per dose.

[0025] The amounts of the isolated SEQ ID NO: 1 or the amino acid sequence that is at least 90% identical thereto and the isolated SEQ ID NO: 2 or the amino acid sequence that is at least 90% identical thereto can be independently selected in such a way that one dose of the vaccine contains the total amount of the Tenacibaculum agent described herein at least 30 micrograms, or at least 35 micrograms, or at least 40 micrograms, or at least 45 micrograms or at least 50 micrograms, or more.

[0026] In certain preferred embodiments, the Tenacibaculum antigen is the isolated amino acid sequence comprising either the isolated SEQ ID NO: 1 or the amino acid sequence that is at least 90% identical thereto or the isolated SEQ ID NO: 2 or the amino acid sequence that is at least 90% identical thereto in the amounts as recited above.DNA vaccines

[0027] In other embodiments, the vaccines disclosed herein are DNA vaccines that contain DNA sequences that encode peptides described above, namely, SEQ ID NO: 1 or the amino acid sequence that is at least 90% (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 1, and / or SEQ ID NO: 2 or the amino acid sequence that is at least 90% (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 2. In both cases, it is preferred that the amino acid sequences differ from the respective reference sequences by conservative substitutions, as described above. In particularly preferred embodiments, the antigen comprises SEQ ID NO: 3 (CAGCAGGCGGCGCCGGCGCTGCCGACCAGCAAAGTGAAAGAAACCGTGGCGTGCACCAAAGGCTATA ACCATAAAGGCCATAGCAAACATACCAGCAGCAACAAAATGAGCCGTGCGAACAGCCCGGATACCTTTG CGGGCTGGGCGAGCTATAGCGGCGCGAACCTGGTGGCGAAACTGAAAGAAACCACCGATTATGATACCAACCTG CGTCCG CTGTTTG ATTATGG CC AGTATG GCGG CAG CCTGTTTAG C AGCACCAAC ATTAAAGCG GTGGCGGATGCGGTGTATAACATGAGCGCGAGCTATGATGGCAGCGAAAGCAGCGGCATGCTGGGCCTGGTGACCTATCTGCATTGCGCGAGCTATCATGAATTTTTTCAGACCGAAGTGACCCTGAACACCAACGC GAAAAGCGCGTATAAACTGGCGGTGAAATATCTGAGCACCAACGCGCGTCTGTGGGATACCACCGAATATGGCCTGGGCGTGCTGGATGAATTTCTGATTATGTGCGATTATGATGGCCTGCGTGATAAAGATTTTGT GCTGAACGTGATTAAAACCGCGATTCGTAACCTGACCGAAAAAGATAACTGGCGTGCGGTGGTGAGCGATCAGCAGATGCTGACCAAATATATTACCGCGTATAACCGTATTTTTTTTCTGATGTTTCGTGGCATGCAG CCGGTGGATGTGGCGTATGAAGCGAGCCTGAACAACGATCCGGAATTTCTGCAGCTGCTGAGCAACCTGGCGACCGATAAAGAACTGCGTACCGAAAACGAAGATCTGGCGCTGATGGTGAACAACGCGATTGGCG AAATGACCCGTACCGCGGATAGCAGCGATGTGCTGAAAGATCAGACCGAACCGTTTATTGCGGAAATTG CGCAGAGCTATGATCGTCTGACCCCGAACTGGTATAAAAGCATTAAAAGCATTAACGAAAGCGGCAACT GCGCGAAATATAACCTGTGCGTGAACATGGATGATATTACCGCGGAAGTGGAAGCGATGCTGTTTCCGA ACACCTTTACCTTTGATGATGGCCGTCTGAAAGTGCGTACCCCGCTGGATTATAAAACCGTGCAGGAACT GTATTATGCGAGCAAACAGGTGCAGACCCAGTTTTTTCGTGCGCTGGCGACCGATGAACCGGTGGCGGGCGATCCGAACCTGAACCTGAACATGGTGGTGTATGGCACCATGAAAAACTATCATGATTGGCAGACCA TTCTGAACGGCCTGGCGACCAACAACGGCGGCATGTATATTGAACGTGGCGCGACCTTTTATACCTATCA GCGTACCTTTACCGAAAGCACCTTTAGCCTGGAAGAACTGTTTCGTCATGAATATGTGCATTATCTGCAGGGCCGTTATATTGCGAACGGCTTTTGGGGCAGCACCGATTTTTATAAAGATGGCCGTCTGATTTGGTTTG AAGAAGGCATGGCGGAACATTTTGCGGGCAGCACCGATAACGATGGCGTGCGTATTCGTGAAAGCCAG GGCAGCAACGTGAAAAACGAAGGCGCGAGCGAATATATGACCGTGAACGAAGTGCTGAACGCGAGCTATGCGGGCGGCTTTAAATTTTATCGTTATGGCAACATGCTGTGGAGCTATTGGTTTAAAAACGATATTAA CACCG CG CGTAAACTG ATTAACCTGGTG CGTG CG G ATG ATGTGG CG GG CTTTG ATACCG A AATTAACCG TCTGGAAAGCGATTATACCCTGCAGGCGAACTATCTGAACTATCTGAACAACGTGGTGATTGATGATAA CAACTGGTGGGAAGTGGTGACCCCGTGGGAAGTGGATGATTTTTTTGTGGTGGGCAACATTGCGGATATTGAAACCGAATTTGAAGCGATTACCAGCAAAGATGTGAGCGTGACCCTGGATGCGAGCACCAGCATTC GTCGTTTTAAAGTGACCGGCAGCCTGAACAGCGGCCAGTTTGAAACCGAACTGAACGATCTGATGACCC AGCTGAAAAGCAGCCCGACCGTGAACAACTTTGATTATATTGGCGGCTATTATAAAGAAGTGAGCGGCA GCAACGCGACCTTTGTGATTACCGGCAGCCTGCGTGATGCGACCGTGAGCGATGCGCCGATTGCGGATT TTACCAGCGATCTGCCGAGCACCATTGTGGGCGGCACCATTCAGTTTACCAACGAAAGCACCGGCTATATTAACAGCTATACCTGGAGCTTTCCGGGCGGCACCCCGAGCACCAGCACCGAAAAAAACCCGATGGTGG TGTATGATACCGCGGGCACCCATAGCGTGACCCTGACCGTGACCAGCGCGAAAAGCGGCAACAACACC CGTACCAAAAACAACTTTATTAAAGTGCATGATAAAAGCACCACCACCTATTGCGATACCAGCCAGGGC GGCACCGGCACCGGCATTATTCGTGTGAACTTTAGCACCCTGGATAACACCAGCGCGCCGCAGAACCCG GCGAACTATAGCGATTATACCAGCTATGCGGCGGAAGTGAAACGTAACAAAACCTATCCGATTACCATT GAAGCGGCGAACACCGCGTGGCCGAACAACGTGGTGAAAGTGTGGATTGATTGGAACCAGAACGGCG ATTTTACCGATGTGGGCGAAGCGGTGTTTAGCTATGAAAAAATTAGCGAAACCGGCAACATTACCATTC CGAGCGATGCGGCGCTGGGCATTACCCGTATGCGTGTGCGTTATGGCTATGGCGATGGCAAAATTCTGG AACCGTGCGGCTATGATGATTATTTTGGCGAAGTGGAAGATTATAGCATTAACGTGGGCATTGCGGCGG CGACCATTACCTGGGCGGGCACCACCAGCACCGATTTTGCGGAAGCGACCAACTGGGATACCAACACCA TTCCGACCAGCTATGATGATGTGATTATTCCGGCGGGCCTGACCAACTATCCGGTGATTAGCACCGCGAC CGAAGTGAAAACCCTGACCATTGCGAGCGGCGCGACCCTGATTGCGAACGCGCCGCTGACCGGCACCG TGACCTATACCCGTAACCTGCCGACCGATAACTGGTATCTGGTGGCGAGCCCGCTGAAATATGAAACCA TTGAACAGCTGAAAAAAAACAACACCTTTGCGAGCGGCACCGGCACCAACATTGGCCTGGCGCCGTATA AAAACAACGGCACCGCGTGGAACTATCTGACCAGCACCAGCAAAGGCAACATTACCAGCGGCCAGGGC TATAG CGTG A AACTG AAAAACG CG GCG AACCTGGTGTTTACCGG CAG CATTAAC AGC ACCGCG GTG AA CTATGGCATTACCAAAGGCGCGAACGATTTTAACCTGATTGGCAACCCGTATACCAGCTATGTGAAACTG GGCGATTTTTTTAAAGATAACGCGACCGGCACCGTGCTGAGCGAAGCGACCATTTGGCTGTGGAACCAG AACACCAACAGCTATGATCTGAAACTGGGCGCGGCGGATGCGAACTATCAGATTGCGCCGGGCCAGGG CTTTTTTGTGAGCGCGAACGCGAACACCCAGGTGACCTTTAGCAAAGAAAACCAGAGCCATCAGAGCGC GACCTTTCAGCGTCAGGCGAAAACCCAGATTAACCTGAGCGTGCGTGAAAACCAGAACAACACCGTGAA AAGCACCAAACTGTATTATCTGAACGGCGTGACCACCGGCTTTGATAACGGCTATGATGGCAGCGTGTT TGGCGGCACCACCACCAACTATGCGCTGTATAGCCAGCTGGTGAGCAACACCAACGGCAAAAACTATGC GGTGCAGAGCCTGCCGATTAACGATCTGGAAAACACCATTGTGCCGATTGGCCTGAAAGCGAAAGCGG GCAAAAAAATTGTGTTTAGCGCGGAAAGCATGAACCTGCCGGAAAACGTGAGCATTTATCTGGAAGATA AACAGAACAACACCTTTACCAACCTGAGCAAAGAAAACTATACCGTGACCCTGACCACCGATGCGAGCC AGGTGGGCCAGTTTTATCTGCATACCAGCAGCAAAGAACTGGATGCGAGCATTCAGACCCCGGCGAGCT TTAGCGAACTGACCGTGTATAAAAGCAGC) and / or SEQ ID NO: 4(TTTTTTAACGCGACCATTAAACATCTGGGCGAACATGCGCATAGCAGCAAAAACCTGGGCGCGGTGAACGGCCTGGCGGAAAAACTGACCGCGACCCTGGCGACCGGCAACGCGGATACCCGTTATAGCGGCACCAAAAGCATTATTACCCGTCTGGTGGGCAACAGCTATGTGCTGCGTGATAACACCCGTGGCGGCGGCGTGAACACCTATAACAGCGGCGCGCAGCCGAGCTATCCGACCACCGATTTTACCGATAGCGATAACAACTGGACCGCGGCGGAATTTAACAACAGCGCGAAAGATAACGCGGCGCTGGATGCGCATTGGGGCGCGGAAATGACCTATGATTATTTTCAGGATAAACATAACCGTAACAGCTATAACGGCAGCGGCGCGACCATTAACAGCTATGTGCATTATGATGATGTGGCGGGCGGCACCGGCTATGATAACGCGTTTTGGAACGGCAGCGTGATGACCTATGGCGATGGCAGCAGCAACGGCAACGAAGGCAACGGCTATTTTGATGCGCTGACCAGCATTGATGTGGCGGCGCATGAAATTGGCCATGCGGTGTGCAGCAACACCGCGAACCTGGCGTATCAGCGTGAAAGCGGCGCGATGAACGAAGGCTTTAGCGATATTTGGGGCGCGGCGGTGGAACATTTTGCGAAAGGCAACGGCAACGATCTGGCGCCGGATGCGAGCGTGTGGCTGATTGGCGATGAAATTGATCGTCGTAACGGCAGCAGCGCGCTGCGTAGCATGAGCAACCCGAACGAACGTAACCAGCCGGATACCTATGGCGGCGTGAACTGGAAAGAACCGAACTGCGGCACCCCGACCCGTAGCAACGATTATTGCGGCGTGCATACCAACAGCGGCGTGCTGAACTATTGGTTTTATCTGCTGACCGTGGGCGGCAGCGGCACCAACGATATTAACAACGCGTTTAACGTGGATGCGATTGGCATGGAAAAAAGCGCGAAAATTAGCTATCGTCTGGAAGCGAACTATCTGAGCGCGAACAGCACCTTTGAAGATGCGCGTGTGGGCAGCATTACCGCGGCGGAAGATCTGTATGGCGCGAACAGCATTGAAGTGCAGAGCGTGACCAACGCGTGGCATGCGGTGGGCGTGGGCCAGGCGTATGTGGAAGATTGCACCCTGGTGGCGCCGAGCAACTTTAACGCGACCAACATTAACGATAACGGCTTTACCGTGACCTGGAGCGCGGTGAGCGAAGCGGTGAGCTATACCGTGACCATTAACGAAATTACCAGCGTGGTGACCGATACCAGCAAAGTGATTACCGGCCTGGTGAGCGGCACCATTTATAACTGCAGCGTGGCGGCGAACTGCGTGAGCGGCGAAGGCGGCACCATTACCAGCAAACTGATTACCACCACCGGCGAAATTCCGCTGAACTATTGCGTGAGCAAAGCGAACAACGTGGCGGATGAATATATTCAGAAAGTGGTGCTGGGCACCATTGATAACACCAGCACCGCGAGCAACGGCTATAGCGATTATACCAGCATTAGCACCAGCCTGATTAAAGGCGAAAGCAACACCATTACCATTACCCCGAAATGGAACGGCACCGTGTATAGCGAAGGCTATGGCGTGTGGATTGATTATAACAAAGATGGCGATTTTGATGATGCGGGCGAAACCGTGTTTACCAAAGCGAAAAGCAAAACCACCCCGATTAACGGCACCTTTACCATTCCGGAAAGCGCGCTGAACGGCGCGACCCGTATGCGTGTGGTGCTGAAATATAACGCGACCCCGACCGCGTGCGAAACCAACATTCAGTATGGCGAAGTGGAAGATTATACCGTGGTGATTGGCGAAGGCAACGCGGATACCACCGCGCCGACCGTGCCGGCGAACCTGGCGGTGAGCAACGTGGATAAAACCAGCGTGACCCTGAACTGGAGCGCGGCGACCGATAACGTGGCGGTGACCGGCTATAACGTGTATCAGGGCGCGACCAAACTGGGCACCACCACCAACATTAGCACCGATATTACCAGCCTGAGCCCGGCGACCAGCTATACCTTTAGCGTGAAAGCGATTGATGCGGTGGCGAACGAAAGCGAAGCGAGCAACG TGATTAACGTGACCACCCTGGCGAACCAGCTGGTGTATTGCGAAAGCAAAGGCACCAACAGCAGCTATG AATGGATTGATGCGGTGAGCCTGGGCGGCATGGCGAACACCAGCGCGAGCAACGGCGGCTATGCGGA TTTTACCAGCAAAATTGCGACCCTGGGCCAGGGCAGCAGCAACGAAATTACCGTGAGCGCGGGCTTTAA AAGCACCGCGTATACCGAACATTGGGCGGTGTGGATTGATTTTAACCAGAACGGCATTTTTGATACCAG CGAAAAAGTGGTGACCGGCGCGAGCAGCAGCAAAGATTATCTGACCAGCACCTTTGAAGTGCCGGCGA GCGCGCTGCTGGGCCAGACCCGTATGCGTGTGAGCATGAAATATAACGCGAGCCAGACCGCGTGCGAA ACCTTTAAAGATGGCGAAGTGGAAGATTATACCGTGAACATTACCGCGACCACCACCAAAGAAGCGCTG CTGAGCGGCAACCGTCTGGTGAACGAACCGAGCACCGCGCTGCAG).

[0028] In the DNA vaccines disclosed herein, the nucleic acid sequences, e.g., SEQ ID NO: 3 and / or SEQ ID NO: 4 are under operable control of a promoter. The promoter may be selected from such exemplary promoters as simian virus 40 early promoter (SV40), cytomegalovirus immediate-early promoter (CMV), human Ubiquitin C promoter (UBC), human elongation factor la promoter (EF1A), mouse phosphoglycerate kinase 1 promoter (PGK), and chicken [3-Actin promoter coupled with CMV early enhancer (CAGG).

[0029] The DNA vaccine disclosed herein may also comprise a polyadenylation signal that terminates transcription of the nucleic acid sequence encoding the antigen.

[0030] Preferably, the nucleic acid sequences disclosed herein (including the promoter, the sequence that encodes the antigen, and the polyadenylation signal) are within a vector. Different vectors suitable for the invention are known in the art, including both plasmid vectors and viral vectors. Suitable plasmids include, without limitations pUC-based vectors, pV AX -vectors, pcDNA- vectors, NTC-vectors. In a set of preferred embodiments, the vector is NTC9385R (Nature Technology Corporation) or a variant thereof, as described in the Examples.

[0031] In other embodiments, a "doggybone" or dbDNA™ plasmid may be used as a vector. dbDNA™ plasmids as well as the process of making these plasmids have been described at least in WQ2018033730, WQ2016034849, WO2019193361, WQ2012017210 and WQ2021161051. The advantage of this approach is that the vector can be synthesized in a cell-free process thus improving manufacturing efficiency. The cell-free process preferably involves amplification of the template via strand displacement replication. This synthesis releases a single stranded DNA,which may in turn be copied into double stranded-DNA, using a polymerase. Alternatively, strand displacement can be achieved by supplying a DNA polymerase and a separate helicase. Replicative helicases may open the duplex DNA and facilitate the advancement of the leadingstrand polymerase. The resulting double-stranded DNA concatemer is enzymatically cut and ligated thus forming the doggybone-like shape DNA construct.

[0032] Suitable viral vectors include, without limitations, alphaviruses such as SAV, rhabdovi ruses such as VHSV and IHNV, paramyxoviruses such as ASPV, adenoviruses, poxviruses such as Salmon gill poxvirus, and the like. These viruses can be genetically modified to remove the parts of the viral genomes responsible for replication. Thus, the resulting viruses would be infectious to fish cells and suitable for production of the antigen, but not be pathogenic.

[0033] Methods of making the amino acid sequences and the nucleic acid sequences disclosed herein are known in the art. For example, the nucleic acid sequences may be designed using software tools, e.g., CLC Main Workbench, and synthesized artificially or generated using targeted mutagenesis. These sequences may be subcloned into expression cassettes and vectors using genetic engineering techniques widely available to one skilled in the art. See, e.g., Molecular cloning: a laboratory manual (Sambrook & Russell: 2000, Cold Spring Harbor Laboratory Press; ISBN: 0879695773), and: Current protocols in molecular biology (Ausubel et al., 1988+ updates, Greene Publishing Assoc., New York; ISBN: 0471625949).Additional antigens

[0034] The vaccines disclosed herein may contain one or more additional antigens as described below. Such antigens may be derived from a bacterial source, from a viral source, from an additional parasitical source, and / or from a fungal source. These additional antigens may be inactivated organisms recited below, or the antigens may be derived from these organisms, including recombinantly prepared antigens.

[0035] Polyvalent vaccines containing antigens from typical fish pathogens other than Tenacibaculum are well known in the art and are already commercially available. In addition, representative isolates of relevant fish pathogens are available from various sources.

[0036] In particular embodiments of the invention said antigen from a bacterial source is selected from the group consisting of: live, attenuated or killed bacteria of the speciesPiscirickettsias sp., Aeromonas sp., Vibrio sp., Aliivibrio sp., Listonella sp., Moritella sp., Pasteurella sp., Photobacterium sp, Flavobacterium sp., Yersinia sp., Renibacterium sp., Streptococcus sp., Lactococcus sp., Leuconostoc sp., Bifidobacterium sp., Pediococcus sp., Brevibacterium sp., Edwarsiella sp., Francisella sp., Pseudomonas sp., Cytophaga sp., Nocardia sp., Mycobacterium sp., parts or subunits of these bacteria, and any combination hereof.

[0037] Isolates of such bacteria are available, e.g. from LGC Promochem / American Type Culture Collection ATCC repository and distribution center (ATCC) including strains of A. salmonicida (ATCC 33658), V. salmonicida (ATCC 43839), V. anguillarum serotype O1(ATCC 43305) and O2(ATCC 19264). In addition, cultures of Piscirickettsias salmonis have been deposited in the European Collection of Cell Culture (ECACC), Health Protection Agency, Porton Down, Salisbury, Wiltshire (UK), SP4 OJG UK on the 9 Jun. 2006 under the following accession numbers: 06050901, 06050902, 06050903 and 07032110.

[0038] Other specific embodiments pertain to a vaccine, wherein said antigenic material obtained from a viral source other than the fish virus as defined above is from a virus selected from the group consisting of: Viral Hemorrhagic Septicemia Virus (VHSV), Infectious Hematopoietic Necrosis virus (IHNV), Infectious Pancreatic Necrosis Virus (IPNV), , Infectious Salmon Anaemia virus (ISAV), Salmon pancreatic disease virus (SPDV), Iridovirus, Nodavirus, Piscine myocarditis virus (PMCV) and heart and skeletal muscle inflammation virus (HSMIV). These antigens may be included as modified live or inactivated organisms, as parts or subunits of any one of these viruses, as DNA vaccines, and / or combinations thereof. Representative species of such viruses are available to the skilled artisan, for instance from the following deposits: infectious pancreatic necrosis virus (IPNV, ATCC VR-1318, country of origin: unknown), Viral Hemorrhagic Septicemia Virus (VHSV, ATCC VR-1389, country of origin: Denmark); Infectious Hematopoietic Necrosis virus (IHNV, ATCC VR-1392, country of origin: USA)); Pancreatic Necrosis Virus; Infectious Salmon Anaemia (ISA) virus (ATCC VR-1554, country of origin: Canada). Patent deposits have previously been made by the present applicant of the following viral species: Heart and Skeletal Muscle Infection Virus (HSMIV, patent deposit nr ECACC 04050401, country of origin: Norway).

[0039] In more specific embodiments, said antigenic material obtained from a viral source other than the fish virus as defined above is from the group consisting of: Glycoprotein of Viral Hemorrhagic Septicemia Virus (VHSV), nucleoprotein of Viral Hemorrhagic Septicemia Virus (VHSV), glycoprotein of Infectious Hematopoietic Necrosis virus (IHNV), nucleoprotein structural proteins of Infectious Pancreatic Necrosis Virus (IPNV), antigenic fragments of any of one of these proteins and combinations hereof.

[0040] In other embodiments said antigenic material from an additional parasitic source is from a source selected from the Lepeophtheirus Sp., Caligus Sp., and Ichthyophthirius Sp, parts of any one of these parasites, and combinations thereof. In yet other embodiments said antigenic material is from a fungal source selected from the group consisting of Saprolegnia Sp., Branchiomyces sanguinis, Branchiomyces demigrans and Icthyophonus hoferi.

[0041] In certain embodiments, the additional antigens to be included into the vaccines described herein are selected form the group consisting of IPNV, ISAV, SPDV, Aeromonas salmonicida, Vibrio anguillarum 01, 02, Vibrio (Aliivibrio) salmonicida, Yersinia ruckeri 01, Renibacterium salmoninarum, Pasteurella atlantica and Moritella viscosa.

[0042] In other embodiments, the additional antigens to be included into the vaccines described herein are selected form the group consisting of IPNV, ISAV, Aeromonas salmonicida, Vibrio anguillarum serotype 1 and 02, Renibacterium salmoninarum, and Vibrio (Aliivibrio) salmonicida.Excipients and adjuvants

[0043] The vaccines of the invention may further comprise a suitable pharmaceutical carrier and / or an adjuvant. The pharmaceutical carriers can be sterile liquids, such as water or buffer solutions, such as saline solutions and aqueous dextrose and glycerol solution. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. Examples of suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E. W. Martin. The formulation should suit the mode of administration.

[0044] The appropriate carrier is evident to those skilled in the art and will depend in large part upon the route of administration. Additional components that may be present in this invention are adjuvants, preservatives, surface active agents, chemical stabilizers, suspending or dispersing agents. Typically, stabilizers, adjuvants and preservatives are optimized to determine the best formulation for efficacy in the target subject.

[0045] In a currently preferred embodiment, the vaccine comprises an adjuvant. Suitable adjuvants include, without limitations, oil. The vaccines disclosed herein may be formulated as oil in water emulsions or, more preferably, water-in-oil emulsions. Other formulations, such as water-in-oil-in-water (W / O / W) may also be prepared.

[0046] The emulsion may optionally contain one or more emulsifiers. Non-natural, synthetic emulsifiers suitable for use in the adjuvant formulations of the present invention include sorbitan-based non-ionic surfactants, e.g. fatty-acid-substituted sorbitan surfactants (commercially available under the name SPAN® or ARLACEL®), fatty acid esters of polyethoxylated sorbitol (TWEEN®), polyethylene glycol esters of fatty acids from sources such as castor oil (EMULFOR®); polyethoxylated fatty acid (e.g., stearic acid available under the name SIMULSOL® M-53), polyethoxylated isooctylphenol / formaldehyde polymer (TYLOXAPOL®), polyoxyethylene fatty alcohol ethers (BRU®); polyoxyethylene nonphenyl ethers (TRITON® N), polyoxyethylene isooctylphenyl ethers (TRITON® X). Preferred synthetic surfactants are the surfactants available underthe name SPAN® and TWEEN®, such as TWEEN®-80 (Polyoxyethylene (20) sorbitan monooleate) and SPAN®-80 (sorbitan monooleate). Adjuvants such as interleukin, salmon interferon, and glycoproteins may also be used.

[0047] In certain embodiments, the adjuvant is a W / O emulsion containing non-mineral oil of vegetable origin and a mannide monooleate emulsifier. See, e.g., MONTANIDE™ ISA adjuvants line from Seppic.

[0048] The vaccine may also comprise a "vehicle". A vehicle is a device to which the antigen adheres, without being covalently bound to it. Such vehicles are biodegradable nano / micro- particles or -capsules of PLGA (poly-lactide-co-glycolic acid), alginate or chitosan, liposomes, niosomes, micelles, multiple emulsions and macrosols, all known in the art. A special form of sucha vehicle, in which the antigen is partially embedded in the vehicle, is the so-called ISCOM (European patents EP 109.942, EP 180.564 and EP 242.380.

[0049] In certain embodiments, the vaccine described herein is formulated as a water-in-oil emulsion. Preferably, the oil is a mineral oil.Methods of use

[0050] The vaccines described herein cn be used for a reduction or prevention of frequency, intensity, or duration of at least one clinical sign of T finnmarkense infection. Symptoms of T finnmarkense include, without limitations, ulcerative lesions on the skin of the fish, hemorrhages and degradation of the fin tissue, weight loss (or failure to gain weight), and increase in mortality. Most preferably, the vaccines disclosed herein decrease mortality induced by T. finnmarkense.

[0051] The vaccines described herein may be administered to the salmonid by a variety of routes, including, without limitation, intraperitoneally, intramuscularly, orally, and by immersion. The route of the administration depends on the formulation. For example, the subunit-based vaccines adjuvanted with a W / O emulsion are preferably administered intraperitoneally. If the vaccine is the DNA vaccine as described above, the route of administration is preferably intramuscular.

[0052] Preferably, the vaccine is administered by an injection in a microdose such that the volume of one dose is under 500 pl, or under 400 pl, or under 300 pl or under 200 pl or about 100 pl or under 100 pl, or about 50 pl or about 25 pl.

[0053] The vaccine disclosed herein may be used in protecting multiple salmonid species against an infection. Suitable salmonids include, without limitations, Atlantic salmon (Salmo salar), coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), sockeye salmon (Oncorhynchus nerka), Chinook salmon (Oncorhynchus tshawytscha) and other species.

[0054] Salmonids of different ages (or weights) may be vaccinated according to the invention. In certain embodiments, the salmonid weighs between about 15 and about 200 grams at the time of vaccination. Thus, the weight of the salmonid at the time of the vaccination may be between about 20 and about 150 grams or between about 40 and about 110 grams or between about 50 and about 100 grams.

[0055] The invention will now be defined in the following non-limiting examples.EXAMPLES

[0056] The aim of this comparative, negative controlled and randomised laboratory experiment was to estimate the efficacy of two experimental T. finnmarkense vaccines assessed in a controlled laboratory study in which vaccinated and unvaccinated Atlantic Salmon were kept together in the same tanks and challenged by bath with T. finnmarkense after an immunisation period of approximately 10 weeks, the last six weeks with 24:0 light. Groups injected with PBS was included as negative controls. The challenge was conducted in sea water.

[0057] The study was conducted in Atlantic salmon (Salma salar) weighing 20-25 grams at the start of the study. The study fish was not vaccinated against any of the antigens in the vaccine, was free from disease the previous month and had a valid health certificate. The fish was not exposed to the pathogens for which efficacy is tested. Sexually matured, injured or deformed fish were excluded from the study during vaccination.Table 1. Environmental parameters

[0058] Blood was sampled from 10 fish at baseline to document absence of antibodies. Heart and kidney were sampled from the same 10 fish on RNAIater®.

[0059] The study groups were acclimatized and vaccinated into six 130 L tanks where they were kept during the immunization and photomanipulation period. The fish were in the same tanks during challenge period. See Table 1 for the summary of the environmental parameters.

[0060] The fish were fed daily according to appetite throughout the study and were taken off feed for a minimum of 24 hours priorto vaccination and challenge. Dead fish were collected daily, marked, frozen and logged. Fish that reached the humane endpoint criteria were humanely euthanized and logged as mortalities, and a comment were reported. Comments were made if the dead fish displayed wounds or other signs of disease atypical to the disease caused by the challenged organism. The fish were frozen in a way that ensures rapid cooling.

[0061] The fish were vaccinated as summarized in Table 2. The vaccines were formulated as Water-in-Oil (W / O) emulsions containing MONTANIDE® ISA 50 V2, containing the antigens (SEQ ID NO: 1 or SEQ ID NO: 2), in at the concentration of 500 micrograms per millilitre. Vaccination was performed by IP injection of 0.1 mL study substance using calibrated SOCOREX® pistol-grip syringes, thus each dose of the vaccine contained 50 micrograms of the antigen. The fish were anesthetized with Tricaine or Benzocaine in association with the vaccination. All fish are VIE tagged in conjunction with the vaccination.Table 2. Study design vaccination*Total of 20 fish for sea water test.

[0062] Fish from tanks A4, A8 and A10 were moved before sea transfer according to Table 3a to free up space for main challenge.

[0063] 10 fish from Tank A9 were used in a smoltification test (exposed to 8°C, Salt Water) before the rest of the fish are transferred to Salt water and challenge was initiated.

[0064] T. finnmarkense isolate HFJ was used as challenge material. Bacteria were grown in 1 liter of marine broth at 16"C until reaching an optical density (OD) of 0.73-0.75 (48-54 hours). Before use, the culture was examined for abnormal bacterial ceil morphology. Small round cells or deviations from typical Tenacibaculum form (long rods) indicate cell death or contamination. The bacterial culture was transferred directly into the infection tanks (8°C seawater) before transferring the fish. Bacterial concentration in the infection tanks was estimated at 1.7-2.2 x 106bacteria / ml.

[0065] The fish were starved for minimum 24 hours prior to the challenge. The challenge was performed as follows: the fish were netted out of one tank and into two 90L buckets containing 60L of aerated water where the challenge was performed. The fish were exposed to the challenge material for a duration of 2 hours, before they were netted back into the tank. The fish flow is described in Table 3b.

[0066] In case of repeated challenge, the fish from cages A2, A5 and A6 were moved back and the challenge in Table 3b was repeated.Table 3a. Transfer of repeated-challenge-fish groups before main challengeTable 3b. Study design main challenge

[0067] The experiments were terminated 3 weeks after challenge.

[0068] Survival curves were plotted using the Kaplan-Meier method, and statistical differences between groups were investigated using the LogRank test (GraphPad Prism v.8.1.1) or similar methods. Statistical significance is defined as p<0.05.

[0069] Accumulated mortality levels were compared between vaccinated groups and controls. The experiments were ended at the discretion of the researchers, but not until at least two consecutive days without mortality in the PBS control group have been recorded. Relativepercentage survival at the time of the end of experiment, (RPSend), was calculated using the following formula:RPSend = (1- (% mortality vaccinated / % mortality control)) x 100%

[0070] The results in the main-challenge and repeated-challenge groups are provided in tables 4A and 4B respectively.Table 4A

[0071] Accordingly, in the main challenge experiment, RPSend for group F01 is = 14.3%, and RPSend for group F02 is 17.95%.Table 4B

[0072] In the repeated challenge experiment, RPSend for group F01 is = 52.94%, and RPSend for group F02 is 88.24%.

[0073] Discrepancies between the main and repeated challenges can arise due to various factors. Notably, the time for antibody development differs. Additionally, minor variations may occur in the fish between the main challenge and repeated challenge, also including the bacterial challenge culture and execution of the challenge procedure etc. Combining the main and repeated challenge experiments, RPS for group F01 is 26.3% and RPS for group F02 is 39.3%.

[0074] All publications cited in the specification, both patent publications and non-patent publications, are indicative of the level of skill of those skilled in the art to which this invention pertains. All these publications are herein fully incorporated by reference to the same extent as if each individual publication were specifically and individually indicated as being incorporated by reference.

[0075] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the following claims.

Claims

CLAIMS1. A vaccine comprising a Tenacibaculum antigen selected from the group consisting of a) an isolated SEQ ID NO: 1 or an amino acid sequence that is at least 90% identical to SEQ ID NO: 1; b) an isolated SEQ ID NO: 2 or an amino acid sequence that is at least 90% identical to SEQ ID NO: 2; or c) a combination of 'a' and 'b'; wherein said vaccine is a W / O emulsion and wherein said Tenacibaculum antigen is present in the amount of at least 30 micrograms per dose.

2. The vaccine according to claim 1, wherein the Tenacibaculum antigen is present in the amount of at least 50 micrograms per dose.

3. The vaccine according to claim 1 or 2, wherein the Tenacibaculum antigen is SEQ ID NO: 1 or 2 or an amino acid sequence that is at least 95% identical thereto.

4. The vaccine of claim 5, wherein the Tenacibaculum antigen is a conservatively substituted variant of SEQ ID NO: 1 or 2.

5. The vaccine according to any one of claims 1-4, wherein the Tenacibaculum antigen is SEQ ID NO: 1.

6. The vaccine according to any one of claims 1-5, further comprising one or more additional antigens.

7. The vaccine of claim 6, wherein said one or more additional antigens are selected from the group consisting of IPNV, ISAV, SPDV, Aeromonas salmonicida, Vibrio anguillarum 01, 02, Vibrio (Aliivibrio) salmonicida, Yersinia ruckeri 01, Renibacterium salmoninarum, Pasteurella atlantica, and Moritella viscosa.

8. The vaccine of claim 6, wherein said one or more additional antigens are selected from the group consisting of IPNV, ISAV, Aeromonas salmonicida, Vibrio anguillarum serotype 1 and 02, and Vibrio (Aliivibrio) salmonicida, Renibacterium salmoninarum, and Piscirickettsia salmonis.

9. Use of the vaccine according to any one of claims 1-8 in protection of salmonids against Tenacibaculum finnmarkense infection.

10. The use according to claim 9, wherein the weight of said salmonid is 20-120 grams.

11. The use according to claim 9 or 10, wherein said salmonid is Atlantic salmon (Salmo salar).

12. The use according to claim 9 or 10, wherein said salmonid is coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), sockeye salmon (Oncorhynchus nerka), Chinook salmon (Oncorhynchus tshawytscha).

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