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

Sandra Vreman*, Joanne McCaffrey, Ditta J. Popma-de Graaf, Hans Nauwynck, Huub F.J. Savelkoul, Anne Moore, Johanna M.J. Rebel, Norbert Stockhofe-Zurwieden

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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™) 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-γ 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-γ level after booster vaccination and an anamnestic antibody response after challenge. Montanide™-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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalVeterinary Immunology and Immunopathology
Volume212
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Porcine respiratory and reproductive syndrome virus
Porcine reproductive and respiratory syndrome virus
Toll-Like Receptors
agonists
adjuvants
Vaccination
Vaccines
vaccines
Inactivated Vaccines
Viremia
skin (animal)
Skin
Antibody Formation
resiquimod
Oils
Swine
Toll-Like Receptor 1
viremia
vaccination
Toll-Like Receptor 2

Keywords

  • Adjuvant
  • PRRSV
  • Skin vaccination
  • Toll-like receptor agonist
  • Vaccine

Cite this

@article{2534e307b2f640b489b56d1b1ac3c285,
title = "Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine",
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™) 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-γ 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-γ level after booster vaccination and an anamnestic antibody response after challenge. Montanide™-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 = "Adjuvant, PRRSV, Skin vaccination, Toll-like receptor agonist, Vaccine",
author = "Sandra Vreman and Joanne McCaffrey and {Popma-de Graaf}, {Ditta J.} and Hans Nauwynck and Savelkoul, {Huub F.J.} and Anne Moore and Rebel, {Johanna M.J.} and Norbert Stockhofe-Zurwieden",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.vetimm.2019.04.008",
language = "English",
volume = "212",
pages = "27--37",
journal = "Veterinary Immunology and Immunopathology",
issn = "0165-2427",
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Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. / Vreman, Sandra; McCaffrey, Joanne; Popma-de Graaf, Ditta J.; Nauwynck, Hans; Savelkoul, Huub F.J.; Moore, Anne; Rebel, Johanna M.J.; Stockhofe-Zurwieden, Norbert.

In: Veterinary Immunology and Immunopathology, Vol. 212, 01.06.2019, p. 27-37.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine

AU - Vreman, Sandra

AU - McCaffrey, Joanne

AU - Popma-de Graaf, Ditta J.

AU - Nauwynck, Hans

AU - Savelkoul, Huub F.J.

AU - Moore, Anne

AU - Rebel, Johanna M.J.

AU - Stockhofe-Zurwieden, Norbert

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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™) 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-γ 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-γ level after booster vaccination and an anamnestic antibody response after challenge. Montanide™-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.

AB - 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™) 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-γ 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-γ level after booster vaccination and an anamnestic antibody response after challenge. Montanide™-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.

KW - Adjuvant

KW - PRRSV

KW - Skin vaccination

KW - Toll-like receptor agonist

KW - Vaccine

U2 - 10.1016/j.vetimm.2019.04.008

DO - 10.1016/j.vetimm.2019.04.008

M3 - Article

VL - 212

SP - 27

EP - 37

JO - Veterinary Immunology and Immunopathology

JF - Veterinary Immunology and Immunopathology

SN - 0165-2427

ER -