PMID- 28778318 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20171226 IS - 1873-2534 (Electronic) IS - 0165-2427 (Linking) VI - 190 DP - 2017 Aug TI - Dendritic cell-targeted porcine reproductive and respiratory syndrome virus (PRRSV) antigens adjuvanted with polyinosinic-polycytidylic acid (poly (I:C)) induced non-protective immune responses against heterologous type 2 PRRSV challenge in pigs. PG - 18-25 LID - S0165-2427(17)30079-X [pii] LID - 10.1016/j.vetimm.2017.07.003 [doi] AB - Porcine Reproductive and Respiratory Syndrome (PRRS) is an economically important swine viral disease worldwide. Current modified live-attenuated vaccines are ineffective against heterologous strains of PRRS virus (PRRSV) circulating in the field. In this study, we evaluated three dendritic cell (DC)-targeted vaccine candidates for their protective efficacy against heterologous PRRSV challenge. Ectodomain regions of DNA-shuffled structural proteins GP3, GP4, GP5 and M of PRRSV were fused together to form the vaccine antigen which was in turn fused with one of three recombinant antibodies each specific to a DC receptor: DC-SIGN, Langerin, and DEC205. The recombinant antibody-fused vaccine antigens were co-administered with polyinosinic-polycytidylic acid (poly (I:C)) adjuvant and subsequently challenged with a heterologous type 2 PRRSV strain (NADC20) in pigs. Our results demonstrate that pigs in DC-SIGN- and DEC205-targeted, but not Langerin- and non-targeted, vaccine groups showed significant IFN-gamma- and IL-4-specific CD4T cell immune responses against the vaccine antigen in 7days post-challenge. Pigs in DC-SIGN- and Langerin-targeted vaccine groups showed greatly reduced IgG responses as compared to the DEC205- and non-targeted vaccine groups. The immune responses induced by DC-targeted vaccines did not reduce viremia and lung pathological lesions in type 2 PRRSV-challenged pigs. In contrast, pigs in Langerin-targeted vaccine group showed significantly increased serum viral titers and viral antigen in lung tissues at 7 and 14days post-challenge respectively. In conclusion, specific targeting of PRRSV antigen through DC-SIGN or DEC205 or Langerin-specific antibodies in the presence of poly (I:C) adjuvant induced immune responses that failed to protect pigs against heterologous type 2 PRRSV challenge. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Subramaniam, Sakthivel AU - Subramaniam S AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Pineyro, Pablo AU - Pineyro P AD - Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA 50011, USA. FAU - Derscheid, Rachel J AU - Derscheid RJ AD - Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA 50011, USA. FAU - Madson, Darin M AU - Madson DM AD - Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA 50011, USA. FAU - Magstadt, Drew R AU - Magstadt DR AD - Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA 50011, USA. FAU - Meng, Xiang-Jin AU - Meng XJ AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. Electronic address: xjmeng@vt.edu. LA - eng PT - Journal Article DEP - 20170710 PL - Netherlands TA - Vet Immunol Immunopathol JT - Veterinary immunology and immunopathology JID - 8002006 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, Viral) RN - 0 (Viral Vaccines) RN - O84C90HH2L (Poly I-C) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Animals MH - Antigens, Viral/*immunology MH - Dendritic Cells/immunology/virology MH - Poly I-C/pharmacology MH - Porcine Reproductive and Respiratory Syndrome/*immunology/prevention & control MH - Porcine respiratory and reproductive syndrome virus/*immunology MH - Swine MH - Viral Vaccines/immunology/*pharmacology OTO - NOTNLM OT - Dendritic cell targeting OT - Porcine DC-SIGN OT - Porcine DEC205 OT - Porcine langerin OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Subunit vaccine EDAT- 2017/08/06 06:00 MHDA- 2017/12/27 06:00 CRDT- 2017/08/06 06:00 PHST- 2017/02/13 00:00 [received] PHST- 2017/06/23 00:00 [revised] PHST- 2017/07/07 00:00 [accepted] PHST- 2017/08/06 06:00 [entrez] PHST- 2017/08/06 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] AID - S0165-2427(17)30079-X [pii] AID - 10.1016/j.vetimm.2017.07.003 [doi] PST - ppublish SO - Vet Immunol Immunopathol. 2017 Aug;190:18-25. doi: 10.1016/j.vetimm.2017.07.003. Epub 2017 Jul 10.