PMID- 33678451 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20210524 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 39 IP - 13 DP - 2021 Mar 26 TI - Early immune responses in skin and lymph node after skin delivery of Toll-like receptor agonists in neonatal and adult pigs. PG - 1857-1869 LID - S0264-410X(21)00176-6 [pii] LID - 10.1016/j.vaccine.2021.02.028 [doi] AB - The skin is potentially an important vaccine delivery route facilitated by a high number of resident antigen presenting cells (APCs), which are known to be stimulated by different Toll-like receptor agonists (TLRa). In this study, neonatal and adult pigs were vaccinated in the skin using dissolving microneedle patches to investigate the immuno-stimulatory potential of different TLRa and possible age-dependent differences early after vaccination. These patches contained TLR1/2a (Pam3Cys), TLR7/8a (R848) or TLR9a (CpG ODN) combined with inactivated porcine reproductive and respiratory syndrome virus (PRRSV) or with an oil-in-water stable emulsion. Vaccinated skin and draining lymph nodes were analysed for immune response genes using microfluidic high-throughput qPCR to evaluate the early immune response and activation of APCs. Skin pathology and immunohistochemistry were used to evaluate the local immune responses and APCs in the vaccinated skin, respectively. In both neonatal and adult pigs, skin vaccination with TLR7/8a induced the most prominent early inflammatory and immune cell responses, particularly in the skin. Skin histopathology and immunohistochemistry of APCs showed comparable results for neonatal and adult pigs after vaccination with the different TLRa vaccines. However, in vaccinated neonatal pigs in the skin and draining lymph node more immune response related genes were upregulated compared to adult pigs. We showed that both neonatal and adult skin could be stimulated to develop an immune response, particularly after TLR7/8a vaccination, with age-dependent differences in regulation of immune genes. Therefore, age-dependent differences in local early immune responses should be considered when developing skin vaccines. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. 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; Cell Biology & Immunology Group, Wageningen University & Research, P.O. Box 338, 6700 HA Wageningen, the Netherlands. Electronic address: Sandra.vreman@wur.nl. FAU - Rebel, Johanna M J AU - Rebel JMJ AD - Wageningen Livestock Research, Wageningen University & Research, the Netherlands. FAU - McCaffrey, Joanne AU - McCaffrey J AD - Xeolas, Pharmaceuticals, Dublin, Ireland. FAU - Ledl, Kristina AU - Ledl K AD - Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS The Hague, the Netherlands. FAU - Arkhipova, Ksenia AU - Arkhipova K AD - Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS The Hague, the Netherlands. FAU - Collins, Damien AU - Collins D AD - Wageningen Livestock Research, Wageningen University & Research, the Netherlands. FAU - McDaid, Dennis AU - McDaid D AD - Wageningen Livestock Research, Wageningen University & Research, 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 - Skovgaard, Kerstin AU - Skovgaard K AD - Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark. FAU - Moore, Anne C AU - Moore AC AD - School of Biochemistry and Cell Biology, School of Pharmacy University College Cork, Cork, Ireland. 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210305 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (Toll-Like Receptors) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Antibodies, Viral MH - Immunity MH - Lymph Nodes MH - *Porcine Reproductive and Respiratory Syndrome MH - *Porcine respiratory and reproductive syndrome virus MH - Swine MH - Toll-Like Receptors MH - Vaccination MH - *Viral Vaccines OTO - NOTNLM OT - Adjuvant OT - Neonatal OT - Skin immunity OT - Skin vaccination OT - Toll-like receptor agonist COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Anne Moore is an inventor of patents that have been or may be licensed to companies developing microneedle-based products. This potential competing interest has been disclosed and is being managed by University College Cork. Dennis McDaid is Chief Operating Officer and current director and owns stock in Xeolas Pharmaceuticals Limited. Joanne McCaffrey and Damien Collins are former employees of Xeolas Pharmaceuticals Limited and had no financial or other competing interests. The other authors have no competing interest to declare.] EDAT- 2021/03/09 06:00 MHDA- 2021/05/25 06:00 CRDT- 2021/03/08 05:36 PHST- 2020/09/26 00:00 [received] PHST- 2021/02/03 00:00 [revised] PHST- 2021/02/10 00:00 [accepted] PHST- 2021/03/09 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2021/03/08 05:36 [entrez] AID - S0264-410X(21)00176-6 [pii] AID - 10.1016/j.vaccine.2021.02.028 [doi] PST - ppublish SO - Vaccine. 2021 Mar 26;39(13):1857-1869. doi: 10.1016/j.vaccine.2021.02.028. Epub 2021 Mar 5.