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Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

Thim HL, Villoing S, McLoughlin M, Christie KE, Grove S, Frost P, Jørgensen JB - Vaccines (Basel) (2014)

Bottom Line: Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced.Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV.The results demonstrate that a combination of pattern recognizing receptor (PRR) ligands, such as CpG/polyI:C, increases both adaptive and innate responses and represents a promising adjuvant strategy for enhancing the protection of future viral vaccines.

View Article: PubMed Central - PubMed

Affiliation: Norwegian College of Fisheries Science, UiT The Arctic University of Norway, Tromsø N-9037, Norway. hanna.l.thim@uit.no.

ABSTRACT
Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR) ligands, such as CpG/polyI:C, increases both adaptive and innate responses and represents a promising adjuvant strategy for enhancing the protection of future viral vaccines.

No MeSH data available.


Related in: MedlinePlus

Relative expression of (A) antiviral, (B) B- and (C) T-cell markers in spleen at 12 and 48 hpv for all treatments compared to saline-treated fish (expression is normalized to reference gene EF1aB). Relative expression is presented as histograms (the colour codes for each gene analysed are indicated below the histograms) calculated from fold induction by Pfaffl’s method (see Materials and Methods), and significant up- or down-regulation is based on data from REST 2009. Significant differences for all treatments compared to SAV Ag are highlighted with an *, against SAV Ag vhsG as Δ and against SAV Ag CpG/polyI:C as °, + or –, respectively, indicates the presence or absence of either SAV Ag, oil, CpG/polyI:C or vhsG.
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vaccines-02-00228-f002: Relative expression of (A) antiviral, (B) B- and (C) T-cell markers in spleen at 12 and 48 hpv for all treatments compared to saline-treated fish (expression is normalized to reference gene EF1aB). Relative expression is presented as histograms (the colour codes for each gene analysed are indicated below the histograms) calculated from fold induction by Pfaffl’s method (see Materials and Methods), and significant up- or down-regulation is based on data from REST 2009. Significant differences for all treatments compared to SAV Ag are highlighted with an *, against SAV Ag vhsG as Δ and against SAV Ag CpG/polyI:C as °, + or –, respectively, indicates the presence or absence of either SAV Ag, oil, CpG/polyI:C or vhsG.

Mentions: Transcription levels of selected antiviral innate genes, as well as selected B- and T-cell markers were analysed at 12 and 48 hpv in HK (Figure 1) and spleen (Figure 2) for the vaccine formulations in relation to the control group. It is worth noting the often high standard deviations underlining the highly individual immunological response, which is common in fish. Tables with average Cq-values are included as supplementary material.


Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

Thim HL, Villoing S, McLoughlin M, Christie KE, Grove S, Frost P, Jørgensen JB - Vaccines (Basel) (2014)

Relative expression of (A) antiviral, (B) B- and (C) T-cell markers in spleen at 12 and 48 hpv for all treatments compared to saline-treated fish (expression is normalized to reference gene EF1aB). Relative expression is presented as histograms (the colour codes for each gene analysed are indicated below the histograms) calculated from fold induction by Pfaffl’s method (see Materials and Methods), and significant up- or down-regulation is based on data from REST 2009. Significant differences for all treatments compared to SAV Ag are highlighted with an *, against SAV Ag vhsG as Δ and against SAV Ag CpG/polyI:C as °, + or –, respectively, indicates the presence or absence of either SAV Ag, oil, CpG/polyI:C or vhsG.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494258&req=5

vaccines-02-00228-f002: Relative expression of (A) antiviral, (B) B- and (C) T-cell markers in spleen at 12 and 48 hpv for all treatments compared to saline-treated fish (expression is normalized to reference gene EF1aB). Relative expression is presented as histograms (the colour codes for each gene analysed are indicated below the histograms) calculated from fold induction by Pfaffl’s method (see Materials and Methods), and significant up- or down-regulation is based on data from REST 2009. Significant differences for all treatments compared to SAV Ag are highlighted with an *, against SAV Ag vhsG as Δ and against SAV Ag CpG/polyI:C as °, + or –, respectively, indicates the presence or absence of either SAV Ag, oil, CpG/polyI:C or vhsG.
Mentions: Transcription levels of selected antiviral innate genes, as well as selected B- and T-cell markers were analysed at 12 and 48 hpv in HK (Figure 1) and spleen (Figure 2) for the vaccine formulations in relation to the control group. It is worth noting the often high standard deviations underlining the highly individual immunological response, which is common in fish. Tables with average Cq-values are included as supplementary material.

Bottom Line: Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced.Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV.The results demonstrate that a combination of pattern recognizing receptor (PRR) ligands, such as CpG/polyI:C, increases both adaptive and innate responses and represents a promising adjuvant strategy for enhancing the protection of future viral vaccines.

View Article: PubMed Central - PubMed

Affiliation: Norwegian College of Fisheries Science, UiT The Arctic University of Norway, Tromsø N-9037, Norway. hanna.l.thim@uit.no.

ABSTRACT
Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR) ligands, such as CpG/polyI:C, increases both adaptive and innate responses and represents a promising adjuvant strategy for enhancing the protection of future viral vaccines.

No MeSH data available.


Related in: MedlinePlus