PMID- 33845333 OWN - NLM STAT- MEDLINE DCOM- 20210927 LR - 20210927 IS - 1873-2542 (Electronic) IS - 0378-1135 (Linking) VI - 256 DP - 2021 May TI - Intradermal co-inoculation of codon pair deoptimization (CPD)-attenuated chimeric porcine reproductive and respiratory syndrome virus (PRRSV) with Toll like receptor (TLR) agonists enhanced the protective effects in pigs against heterologous challenge. PG - 109048 LID - S0378-1135(21)00071-7 [pii] LID - 10.1016/j.vetmic.2021.109048 [doi] AB - The objective of this study was to assess protective efficacy of vaccination using CPD-attenuated chimeric PRRSV and Toll like receptor (TLR) agonists (HSP70 c-terminal domain and HSPX) as adjuvants through different inoculation routes. In this study, a chimeric PRRSV composed of two field isolates was synthesized and attenuated by CPD in NSP1 as described in the previous study. The infection of the CPD-attenuated chimeric PRRSV to pigs of 3 weeks-old showed no clinical signs without pathological lesions in necropsy, while it induced improved cross immunity between its parent strains. The TLR agonists were expressed in E. coli and purified to be used. In challenge experiment, pigs of 3 weeks-old were vaccinated using the CPD-attenuated chimeric virus with the prepared TLR agonists through intramuscular or intradermal route, following heterologous challenge after 4 weeks of vaccination. In results, intramuscular or intradermal inoculation of the CPD-attenuated chimeric virus demonstrated excellent protective efficacy against heterologous challenges. Importantly, intradermal inoculation with the TLR agonists enhanced protective effects as shown in the significantly increased level of PRRSV-specific IFN-gamma-SCs and cytokines in sera, and the significant reduction of pathological lesion and viral load in lung. This study suggested that the intradermal inoculation of CPD-attenuated chimeric PRRSV plus TLR agonists should be more effective for protection of pigs against diverse PRRS field viruses. CI - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Park, Changhoon AU - Park C AD - Department of Microbiology and Immunology, Eulji University School of Medicine, Yongdu-dong, Jung-gu, Daejeon, Republic of Korea. FAU - Lee, Myung-Shin AU - Lee MS AD - Department of Microbiology and Immunology, Eulji University School of Medicine, Yongdu-dong, Jung-gu, Daejeon, Republic of Korea. FAU - Baek, Jong Hyuk AU - Baek JH AD - Department of Animal Vaccine Development, BioPOA, 593-26 Dongtangiheung-ro, Hwaseong-si, Gyeonggi-do, Republic of Korea. FAU - Cho, Sun Hee AU - Cho SH AD - Department of Animal Vaccine Development, BioPOA, 593-26 Dongtangiheung-ro, Hwaseong-si, Gyeonggi-do, Republic of Korea. FAU - Hyun, Bang-Hun AU - Hyun BH AD - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea. FAU - You, Su-Hwa AU - You SH AD - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea. FAU - Cha, Sang-Ho AU - Cha SH AD - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea. Electronic address: virusmania@korea.kr. LA - eng PT - Comparative Study PT - Journal Article DEP - 20210323 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cytokines) RN - 0 (Toll-Like Receptors) RN - 0 (Vaccines, Attenuated) RN - 0 (Viral Vaccines) SB - IM MH - Adjuvants, Immunologic MH - Animals MH - Animals, Newborn MH - Chimera MH - Cytokines MH - Escherichia coli/genetics/metabolism MH - Injections, Intradermal/veterinary MH - Porcine Reproductive and Respiratory Syndrome/*prevention & control/virology MH - Porcine respiratory and reproductive syndrome virus/genetics/*immunology MH - Swine MH - Toll-Like Receptors/drug effects/genetics/metabolism MH - Vaccination/*veterinary MH - Vaccines, Attenuated/administration & dosage MH - Viral Vaccines/*administration & dosage OTO - NOTNLM OT - Chimera OT - Codon-pair deoptimization OT - Porcine reproductive and respiratory syndrome virus OT - Toll like receptor (TLR) agonists OT - Vaccine EDAT- 2021/04/13 06:00 MHDA- 2021/09/28 06:00 CRDT- 2021/04/12 20:21 PHST- 2020/12/10 00:00 [received] PHST- 2021/03/19 00:00 [accepted] PHST- 2021/04/13 06:00 [pubmed] PHST- 2021/09/28 06:00 [medline] PHST- 2021/04/12 20:21 [entrez] AID - S0378-1135(21)00071-7 [pii] AID - 10.1016/j.vetmic.2021.109048 [doi] PST - ppublish SO - Vet Microbiol. 2021 May;256:109048. doi: 10.1016/j.vetmic.2021.109048. Epub 2021 Mar 23.