PMID- 33383553 OWN - NLM STAT- MEDLINE DCOM- 20210706 LR - 20210706 IS - 1873-2534 (Electronic) IS - 0165-2427 (Linking) VI - 232 DP - 2021 Feb TI - Immune responses induced by inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in neonatal pigs using different adjuvants. PG - 110170 LID - S0165-2427(20)30196-3 [pii] LID - 10.1016/j.vetimm.2020.110170 [doi] AB - Vaccination of neonatal pigs could be supportive to prevent porcine reproductive and respiratory syndrome virus (PRRSV), which is an important porcine pathogen causing worldwide welfare and health problems in pigs of different age classes. However, neonatal immunity substantially differs to adults, thus different vaccines may be required in neonateal pigs. We examined if the immunogenicity and efficacy of inactivated PRRSV (iPRRSV) vaccines in neonatal pigs could be improved with adjuvants containing oil-in water (O/W) emulsions with or without Toll-like receptor (TLR) agonists and by altering the delivery route from intramuscular (i.m.) to the skin. Three-day-old PRRSV-naive piglets (n = 54, divided in 6 groups) received a prime vaccination and a booster vaccination four weeks later. The vaccine formulations consisted of different O/W emulsions (Montanide ISA28RVG (ISA28)), a squalene in water emulsion (SWE) for i.m. or a Stable Emulsion (SE) with squalene for skin vaccination) and/or a mixture of TLR1/2, 7/8 and 9 agonists (TLRa) combined with iPRRSV strain 07V063. These vaccines were delivered either i.m. (ISA28, SWE, TLRa or SWE + TLRa) or into the skin (skiSE + TLRa) with dissolving microneedle (DMN)-patches. All animals received a challenge with homologous PRRSV three weeks after booster vaccination. Specific antibodies, IFN-gamma production and viremia were measured at several time-points after vaccination and/or challenge, while lung pathology was studied at necropsy. After booster vaccination, only ISA28 induced a specific antibody response while a specific T-cell IFN-gamma response was generated in the SWE group, that was lower for ISA28, and absent in the other groups. This suggests that prime vaccination in neonates induced a specific immune response after booster vaccination, dependent on the emulsion formulation, but not dependent on the presence of the TLRa or delivery route. Despite the measured immune responses none of the vaccines showed any efficacy. Further research focused on the early immune response in draining lymph nodes is needed to elucidate the potential of TLR agonists in vaccines for neonatal pigs. CI - Copyright (c) 2020 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Vreman, Sandra AU - Vreman S AD - Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, the Netherlands. Electronic address: sandra.vreman@wur.nl. FAU - Stockhofe-Zurwieden, Norbert AU - Stockhofe-Zurwieden N AD - Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, the Netherlands. FAU - Popma-de Graaf, Ditta J AU - Popma-de Graaf DJ AD - Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, the Netherlands. FAU - Savelkoul, Huub F J AU - Savelkoul HFJ AD - Cell Biology & Immunology Group, Wageningen University & Research P.O. Box 338, 6700 HA, Wageningen, the Netherlands. FAU - Barnier-Quer, C AU - Barnier-Quer C AD - Vaccine Formulation Laboratory, University of Lausanne, Epalinges, Switzerland. FAU - Collin, N AU - Collin N AD - Vaccine Formulation Laboratory, University of Lausanne, Epalinges, Switzerland. FAU - Collins, Damien AU - Collins D AD - Xeolas, Pharmaceuticals, Dublin, Ireland. FAU - McDaid, Dennis AU - McDaid D AD - Xeolas, Pharmaceuticals, Dublin, Ireland. FAU - Moore, Anne C AU - Moore AC AD - School of Biochemistry and Cell Biology, School of Pharmacy, University College Cork, Cork, Ireland. FAU - Rebel, Johanna M J AU - Rebel JMJ AD - Wageningen Livestock Research, Wageningen University & Research, the Netherlands. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary DEP - 20201215 PL - Netherlands TA - Vet Immunol Immunopathol JT - Veterinary immunology and immunopathology JID - 8002006 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cytokines) RN - 0 (Vaccines, Inactivated) RN - 0 (Viral Vaccines) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Animals MH - Animals, Newborn MH - Cytokines/blood MH - Immunity, Cellular MH - *Immunogenicity, Vaccine MH - Lung/pathology MH - Lymphocytes/immunology MH - Male MH - Porcine Reproductive and Respiratory Syndrome/immunology/pathology/*prevention & control MH - Porcine respiratory and reproductive syndrome virus/*immunology MH - Swine MH - Vaccines, Inactivated/immunology MH - Viral Vaccines/*immunology MH - Viremia/veterinary OTO - NOTNLM OT - Adjuvant OT - Neonatal pig OT - PRRSV OT - Skin vaccination OT - Toll-like receptor agonist EDAT- 2021/01/01 06:00 MHDA- 2021/07/07 06:00 CRDT- 2020/12/31 20:17 PHST- 2019/10/08 00:00 [received] PHST- 2020/12/12 00:00 [revised] PHST- 2020/12/13 00:00 [accepted] PHST- 2021/01/01 06:00 [pubmed] PHST- 2021/07/07 06:00 [medline] PHST- 2020/12/31 20:17 [entrez] AID - S0165-2427(20)30196-3 [pii] AID - 10.1016/j.vetimm.2020.110170 [doi] PST - ppublish SO - Vet Immunol Immunopathol. 2021 Feb;232:110170. doi: 10.1016/j.vetimm.2020.110170. Epub 2020 Dec 15.