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

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dc.contributor.authorVreman, Sandra
dc.contributor.authorMcCaffrey, Joanne
dc.contributor.authorPopma-de Graaf, Ditta J.
dc.contributor.authorNauwynck, Hans
dc.contributor.authorSavelkoul, Huub F. J.
dc.contributor.authorMoore, Anne C.
dc.contributor.authorRebel, Johanna M. J.
dc.contributor.authorStockhofe-Zurwieden, Norbert
dc.contributor.funderHorizon 2020en
dc.date.accessioned2019-09-17T14:47:10Z
dc.date.available2019-09-17T14:47:10Z
dc.date.issued2019-04-30
dc.description.abstractToll-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.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationVreman, S., McCaffrey, J., Popma-de Graaf, D. J., Nauwynck, H., Savelkoul, H. F. J., Moore, A. C., Rebel, J. M. J. and 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, pp. 27-37. (10pp.) DOI: 10.1016/j.vetimm.2019.04.008en
dc.identifier.doi10.1016/j.vetimm.2019.04.008en
dc.identifier.eissn1873-2534
dc.identifier.endpage37en
dc.identifier.issn0165-2427
dc.identifier.journaltitleVeterinary Immunology and Immunopathologyen
dc.identifier.startpage27en
dc.identifier.urihttps://hdl.handle.net/10468/8549
dc.identifier.volume212en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/633184/EU/Strengthening Animal Production and Health through the Immune Response/SAPHIRen
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0165242719300406?via%3Dihub
dc.rights©2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND licence (http://creativecommons.org/licences/BY-NY-ND/4.0/).en
dc.rights.urihttp://creativecommons.org/licences/BY-NY-ND/4.0/en
dc.subjectPRRSVen
dc.subjectVaccineen
dc.subjectAdjuvanten
dc.subjectToll-like receptor agonisten
dc.subjectSkin vaccinationen
dc.titleToll-like receptor agonists as adjuvants for inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccineen
dc.typeArticle (peer-reviewed)en
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