PMID- 31213249
OWN - NLM
STAT- MEDLINE
DCOM- 20190808
LR  - 20190808
IS  - 1873-2534 (Electronic)
IS  - 0165-2427 (Linking)
VI  - 212
DP  - 2019 Jun
TI  - Toll-like receptor agonists as adjuvants for inactivated porcine reproductive and 
      respiratory syndrome virus (PRRSV) vaccine.
PG  - 27-37
LID - S0165-2427(19)30040-6 [pii]
LID - 10.1016/j.vetimm.2019.04.008 [doi]
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-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-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.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Vreman, Sandra
AU  - Vreman S
AD  - Wageningen Bioveterinary Research, Wageningen University & Research, the 
      Netherlands; Cell Biology & Immunology group, Wageningen University & Research, 
      the Netherlands. Electronic address: Sandra.vreman@wur.nl.
FAU - McCaffrey, Joanne
AU  - McCaffrey J
AD  - Xeolas, Pharmaceuticals, Dublin, Ireland.
FAU - Popma-de Graaf, Ditta J
AU  - Popma-de Graaf DJ
AD  - Wageningen Bioveterinary Research, Wageningen University & Research, the 
      Netherlands.
FAU - Nauwynck, Hans
AU  - Nauwynck H
AD  - Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 
      Belgium.
FAU - Savelkoul, Huub F J
AU  - Savelkoul HFJ
AD  - Cell Biology & Immunology group, Wageningen University & Research, the 
      Netherlands.
FAU - Moore, Anne
AU  - Moore A
AD  - School of Pharmacy, School of Biochemistry and Cell Biology, University College 
      Cork, Cork, Ireland.
FAU - Rebel, Johanna M J
AU  - Rebel JMJ
AD  - Wageningen Livestock Research, Wageningen University & Research, the Netherlands.
FAU - Stockhofe-Zurwieden, Norbert
AU  - Stockhofe-Zurwieden N
AD  - Wageningen Bioveterinary Research, Wageningen University & Research, the 
      Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20190430
PL  - Netherlands
TA  - Vet Immunol Immunopathol
JT  - Veterinary immunology and immunopathology
JID - 8002006
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Cytokines)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Vaccines, Inactivated)
RN  - 0 (Viral Vaccines)
MH  - Adjuvants, Immunologic/*administration & dosage
MH  - Animals
MH  - Antibodies, Viral/blood
MH  - Cytokines/blood/immunology
MH  - Male
MH  - Oligodeoxyribonucleotides/administration & dosage/*immunology
MH  - Porcine Reproductive and Respiratory Syndrome/immunology/*prevention & control
MH  - Porcine respiratory and reproductive syndrome virus
MH  - Swine
MH  - Toll-Like Receptor 9/*agonists/immunology
MH  - Vaccination
MH  - Vaccines, Inactivated/immunology
MH  - Viral Vaccines/*immunology
MH  - Viremia
OTO - NOTNLM
OT  - Adjuvant
OT  - PRRSV
OT  - Skin vaccination
OT  - Toll-like receptor agonist
OT  - Vaccine
EDAT- 2019/06/20 06:00
MHDA- 2019/08/09 06:00
CRDT- 2019/06/20 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/03/21 00:00 [revised]
PHST- 2019/04/27 00:00 [accepted]
PHST- 2019/06/20 06:00 [entrez]
PHST- 2019/06/20 06:00 [pubmed]
PHST- 2019/08/09 06:00 [medline]
AID - S0165-2427(19)30040-6 [pii]
AID - 10.1016/j.vetimm.2019.04.008 [doi]
PST - ppublish
SO  - Vet Immunol Immunopathol. 2019 Jun;212:27-37. doi: 10.1016/j.vetimm.2019.04.008. 
      Epub 2019 Apr 30.