Abstract
A previous study showed that a plasmid expressing IFNa (pIFNa) strongly enhanced protection and antibody production of a DNA vaccine against infectious salmon anemia virus (ISAV) in Atlantic salmon. The vaccine consisted of a plasmid (pHE) expressing the virus hemagglutinin-esterase as an antigen. To increase the understanding of the adjuvant effect of pIFNa, we here compared transcriptome responses in salmon muscle at the injection site at week 1 and 2 after injection of pIFNa, pHE, plasmid control (pcDNA3.3) and PBS, respectively. The results showed that the IFNa plasmid mediates an increase in gene transcripts of at least three major types in the muscle; typical IFN-I induced genes (ISGs), certain chemokines and markers of B- cells, T-cells and antigen-presenting cells. The latter suggests recruitment of cells to the plasmid injection site. Attraction of lymphocytes was likely caused by the induction of chemokines homologous to mammalian CCL5, CCL8, CCL19 and CXCL10. IFN may possibly also co-stimulate activation of lymphocytes as suggested by studies in mammals. A major finding was that both pcDNA3.3 and pHE caused responses similar to pIFNa, but at lower magnitude. Plasmid DNA may thus by itself have adjuvant activity as observed in mammalian models. Notably, pHE had a lower effect on many immune genes including ISGs and chemokines than pcDNA3.3, which suggests an inhibitory effect of HE expression on the immune genes. This hypothesis was supported by an Mx-reporter assay. The present study thus suggests that a main role for pIFNa as adjuvant in the DNA vaccine against ISAV may be to overcome the inhibitory effect of HE- expression on plasmid-induced ISGs and chemokines.
Highlights
A previous study showed that Atlantic salmon type I interferons (IFNs) possess potent adjuvant effect in combination with a DNA vaccine against infectious salmon anemia virus (ISAV) based on the viral hemagglutinin-esterase (HE) as antigen [1]
Treatment of fish with plasmids pcDNA3.3 encoding the open reading frame (ORF) of Atlantic salmon IFNa1 and pcDNA3.3 plasmid without insert were available from a previous study [10]. pcDNA3.3 encoding hemagglutinin-esterase from infectious salmon anemia virus was obtained by Transcriptome analysis of ISAV DNA vaccine with IFN as adjuvant subcloning from a construct used previously and is named plasmid expressing HE (pHE) [1]
The number of differentially expressed genes (DEG) increased from week 1 (W1) to week 2 (W2) in all the three groups of fish injected with plasmid (Fig 1A)
Summary
A previous study showed that Atlantic salmon type I interferons (IFNs) possess potent adjuvant effect in combination with a DNA vaccine against infectious salmon anemia virus (ISAV) based on the viral hemagglutinin-esterase (HE) as antigen [1]. Transcriptome analysis of ISAV DNA vaccine with IFN as adjuvant form of salaries for author AK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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