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Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine

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Abstract
Toll-like receptor (TLR) agonists can effectively stimulate antigen-presenting cells (APCs) and are anticipated to be promising adjuvants in combination with inactivated vaccines. In this study, the adjuvant potential of three different TLR-agonists were compared with an oil-in-water (O/W) adjuvant in combination with inactivated porcine reproductive and respiratory syndrome virus (iPRRSV) applied by different administration routes: intramuscular (i.m.) or into the skin using dissolving microneedle (DMN) patches. Pigs received a prime vaccination followed by a booster vaccination four weeks later. TLR1/2 (Pam3Cys), TLR7/8 (R848) or TLR9 (CpG ODN) agonists were used as adjuvant in combination with iPRRSV strain 07V063. O/W adjuvant (Montanide (TM)) was used as reference control adjuvant and one group received a placebo vaccination containing diluent only. All animals received a homologous challenge with PRRSV three weeks after the booster vaccination. Antibody and IFN-gamma production, serum cytokines and viremia were measured at several time-points after vaccination and/or challenge, and lung pathology at necropsy. Our results indicate that a TLR 1/2, 7/8 or 9 agonist as adjuvant with iPRRSV does not induce a detectable PRRSV-specific immune response, independent of the administration route. However, the i.m. TLR9 agonist group showed reduction of viremia upon challenge compared to the non-vaccinated animals, supported by a non-antigen-specific IFN-gamma level after booster vaccination and an anamnestic antibody response after challenge. Montanide (TM)-adjuvanted iPRRSV induced antigen-specific immunity after booster combined with reduction of vireamia. Skin application of TLR7/8 agonist, but not the other agonists, induced a local skin reaction. Further research is needed to explore the potential of TLR agonists as adjuvants for inactivated porcine vaccines with a preference for TLR9 agonists.
Keywords
IMMUNE-RESPONSES, CPG OLIGODEOXYNUCLEOTIDE, INTRADERMAL VACCINATION, EUROPEAN GENOTYPE, SUBUNIT VACCINES, DENDRITIC CELLS, PIGS, INFECTION, EFFICACY, DISEASE, PRRSV, Vaccine, Adjuvant, Toll-like receptor agonist, Skin vaccination

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MLA
Vreman, Sandra, et al. “Toll-like Receptor Agonists as Adjuvants for Inactivated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine.” VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, vol. 212, 2019, pp. 27–37.
APA
Vreman, S., McCaffrey, J., Popma-de Graaf, D. J., Nauwynck, H., Savelkoul, H. F., Moore, A., … Stockhofe-Zurwieden, N. (2019). Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 212, 27–37.
Chicago author-date
Vreman, Sandra, Joanne McCaffrey, Ditta J Popma-de Graaf, Hans Nauwynck, Huub FJ Savelkoul, Anne Moore, Johanna MJ Rebel, and Norbert Stockhofe-Zurwieden. 2019. “Toll-like Receptor Agonists as Adjuvants for Inactivated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine.” VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 212: 27–37.
Chicago author-date (all authors)
Vreman, Sandra, Joanne McCaffrey, Ditta J Popma-de Graaf, Hans Nauwynck, Huub FJ Savelkoul, Anne Moore, Johanna MJ Rebel, and Norbert Stockhofe-Zurwieden. 2019. “Toll-like Receptor Agonists as Adjuvants for Inactivated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine.” VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 212: 27–37.
Vancouver
1.
Vreman S, McCaffrey J, Popma-de Graaf DJ, Nauwynck H, Savelkoul HF, Moore A, et al. Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY. 2019;212:27–37.
IEEE
[1]
S. Vreman et al., “Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine,” VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, vol. 212, pp. 27–37, 2019.
@article{8649981,
  abstract     = {{Toll-like receptor (TLR) agonists can effectively stimulate antigen-presenting cells (APCs) and are anticipated to be promising adjuvants in combination with inactivated vaccines. In this study, the adjuvant potential of three different TLR-agonists were compared with an oil-in-water (O/W) adjuvant in combination with inactivated porcine reproductive and respiratory syndrome virus (iPRRSV) applied by different administration routes: intramuscular (i.m.) or into the skin using dissolving microneedle (DMN) patches. Pigs received a prime vaccination followed by a booster vaccination four weeks later. TLR1/2 (Pam3Cys), TLR7/8 (R848) or TLR9 (CpG ODN) agonists were used as adjuvant in combination with iPRRSV strain 07V063. O/W adjuvant (Montanide (TM)) was used as reference control adjuvant and one group received a placebo vaccination containing diluent only. All animals received a homologous challenge with PRRSV three weeks after the booster vaccination. Antibody and IFN-gamma production, serum cytokines and viremia were measured at several time-points after vaccination and/or challenge, and lung pathology at necropsy. Our results indicate that a TLR 1/2, 7/8 or 9 agonist as adjuvant with iPRRSV does not induce a detectable PRRSV-specific immune response, independent of the administration route. However, the i.m. TLR9 agonist group showed reduction of viremia upon challenge compared to the non-vaccinated animals, supported by a non-antigen-specific IFN-gamma level after booster vaccination and an anamnestic antibody response after challenge. Montanide (TM)-adjuvanted iPRRSV induced antigen-specific immunity after booster combined with reduction of vireamia. Skin application of TLR7/8 agonist, but not the other agonists, induced a local skin reaction. Further research is needed to explore the potential of TLR agonists as adjuvants for inactivated porcine vaccines with a preference for TLR9 agonists.}},
  author       = {{Vreman, Sandra and McCaffrey, Joanne and Popma-de Graaf, Ditta J and Nauwynck, Hans and Savelkoul, Huub FJ and Moore, Anne and Rebel, Johanna MJ and Stockhofe-Zurwieden, Norbert}},
  issn         = {{0165-2427}},
  journal      = {{VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}},
  keywords     = {{IMMUNE-RESPONSES,CPG OLIGODEOXYNUCLEOTIDE,INTRADERMAL VACCINATION,EUROPEAN GENOTYPE,SUBUNIT VACCINES,DENDRITIC CELLS,PIGS,INFECTION,EFFICACY,DISEASE,PRRSV,Vaccine,Adjuvant,Toll-like receptor agonist,Skin vaccination}},
  language     = {{eng}},
  pages        = {{27--37}},
  title        = {{Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine}},
  url          = {{http://dx.doi.org/10.1016/j.vetimm.2019.04.008}},
  volume       = {{212}},
  year         = {{2019}},
}

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