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dc.date.accessioned2016-03-15T10:18:50Z
dc.date.available2016-03-15T10:18:50Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10852/49842
dc.description.abstractNon-living antigens are often poorly immunogenic and require addition of adjuvants to elicit protective immunity. Due to the immunostimulatory potential of Toll-like receptor (TLR) ligands, they are explored as vaccine adjuvants. The development of efficient and cheap vaccines against aquatic viruses is important for a sustainable aquaculture industry and the adjuvants for fish vaccines need to be improved. However, increased knowledge of fish TLR function is required before their ligands can find their way into fish vaccines. The major aim if this thesis has been to contribute to a more detailed understanding of fish TLRs. First, the tissue distribution of all known Atlantic salmon TLRs, the immunostimulatory potential of a panel of TLR ligands in primary head kidney leucocytes, and the impact of viral infection on TLR expression in head kidney were investigated. Head kidney and spleen were the main TLR expressing organs in Atlantic salmon. Several TLR ligands induced expression of inflammatory cytokines in salmon head kidney leucocytes. TLR3, TLR7, and TLR8a1 were induced in vivo after viral infection. In order to functionally validate ligand-specific activation of fish TLRs, we established an in vitro reporter assay in a salmon cell line. However, classical TLR2 ligands failed to activate rainbow trout TLR2 signalling when using NF-?B activation as measure of activation. To test the in vivo immunostimulatory potential of a TLR ligand alone and in vaccine formulations, a cold-water zebrafish challenge model was used. The TLR3 ligand poly I:C induced expression of antiviral transcripts in zebrafish head kidney and pre-treatment with poly I:C delayed VHSV (viral haemorrhagic septicaemia virus)-induced mortality. Chitosan encapsulated poly I:C was demonstrated to provide protection against VHSV when co-injected with two different non-living antigens (inactivated whole VHSV and VHSV glycoprotein G). Due to decreasing levels of the dietary n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in Atlantic salmon feed, we investigated how minimal levels of these fatty acids affect TLR signalling in Atlantic salmon leucocytes. The ability of leucocytes to respond to TLR ligand stimuli was reduced with low dietary- and head kidney levels of EPA and DHA, indicating the importance of n- 3 fatty acids in resistance to infection and response to vaccines. Our results provide new knowledge in the fish TLR field and lend support to poly I:C as a promising adjuvant candidate in viral vaccines.en_US
dc.language.isoenen_US
dc.relation.haspartPaper I: Effects of TLR agonists and viral infection on cytokine and TLR expression in Atlantic salmon (Salmo salar). Arnemo M, Kavaliauskis A, Gjøen T. Developmental and Comparative Immunology (2014). 46, 139-145. The paper is not available in DUO due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.dci.2014.03.023
dc.relation.haspartPaper II: Structurally diverse genes encode Tlr2 in rainbow trout: The conserved receptor cannot be stimulated by classical ligands to activate NF-kappaB in vitro. Brietzke A, Arnemo M, Gjøen T, Rebl H, Korytár T, Goldammer T, Rebl A, Seyfert HM. Developmental and Comparative Immunology (2016). 54, 75-88. The paper is not available in DUO due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.dci.2015.08.012
dc.relation.haspartPaper III: Use of poly I:C stabilised with chitosan as a vaccine-adjuvant against Viral Haemorrhagic Septicaemia Virus infection in zebrafish. Kavaliauskis A, Arnemo M, Kim SH, Ulanova L, Speth M, Novoa B, Dios S, Evensen Ø, Griffiths GW, Gjøen T. Zebrafish (2015). 12, 421-431. The paper is not available in DUO due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1089/zeb.2015.1126
dc.relation.haspartPaper IV: Chitosan-poly I:C nanoparticles: a novel adjuvant in aquaculture vaccines. A study of particle bio- distribution and immune response in zebrafish (Danio rerio). Kavaliauskis A, Arnemo M, Speth MT, Lagos Rojas LX, Rishovd AL, Estepa A, Griffiths G, Gjøen T. Manuscript submitted for publication. To be published. The paper is not available in DUO awaiting publishing.
dc.relation.haspartPaper V: Effects of dietary n-3 fatty acids on Toll-like receptor activation in primary leucocytes from Atlantic salmon (Salmo salar). Arnemo M, Kavaliauskis A, Mira MB, Berge GM, Ruyter B, Gjøen T. Manuscript submitted for publication. To be published. The paper is not available in DUO awaiting publishing.
dc.relation.urihttp://dx.doi.org/10.1016/j.dci.2014.03.023
dc.relation.urihttp://dx.doi.org/10.1016/j.dci.2015.08.012
dc.relation.urihttp://dx.doi.org/10.1089/zeb.2015.1126
dc.titleThe use of Toll-like receptor ligands as adjuvants in fish vaccinesen_US
dc.typeDoctoral thesisen_US
dc.creator.authorArnemo, Marianne
dc.identifier.urnURN:NBN:no-53560
dc.type.documentDoktoravhandlingen_US
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/49842/1/PhD-Arnemo-DUO.pdf


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