PMID- 25446829 OWN - NLM STAT- MEDLINE DCOM- 20150723 LR - 20181202 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 32 IP - 50 DP - 2014 Nov 28 TI - In vivo targeting of porcine reproductive and respiratory syndrome virus antigen through porcine DC-SIGN to dendritic cells elicits antigen-specific CD4T cell immunity in pigs. PG - 6768-75 LID - S0264-410X(14)01365-6 [pii] LID - 10.1016/j.vaccine.2014.10.005 [doi] AB - Immunogenicity of protein subunit vaccines may be dramatically improved by targeting them through antibodies specific to c-type lectin receptors (CLRs) of dendritic cells in mice, cattle, and primates. This novel vaccine development approach has not yet been explored in pigs or other species largely due to the lack of key reagents. In this study, we demonstrate that porcine reproductive and respiratory syndrome virus (PRRSV) antigen was targeted efficiently to dendritic cells through antibodies specific to a porcine CLR molecule DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) in pigs. A recombinant PRRSV antigen (shGP45M) was constructed by fusing secretory-competent subunits of GP4, GP5 and M proteins derived from genetically-shuffled strains of PRRSV. In vaccinated pigs, when the PRRSV shGP45M antigen was delivered through a recombinant mouse-porcine chimeric antibody specific to the porcine DC-SIGN (pDC-SIGN) neck domain, porcine dendritic cells rapidly internalized them in vitro and induced higher numbers of antigen-specific interferon-gamma producing CD4T cells compared to the pigs receiving non-targeted PRRSV shGP45M antigen. The pDC-SIGN targeting of recombinant antigen subunits may serve as an alternative or complementary strategy to existing vaccines to improve protective immunity against PRRSV by inducing efficient T cell responses. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Subramaniam, Sakthivel AU - Subramaniam S AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Pineyro, Pablo AU - Pineyro P AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Tian, Debin AU - Tian D AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Overend, Christopher AU - Overend C AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Yugo, Danielle M AU - Yugo DM AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Matzinger, Shannon R AU - Matzinger SR AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Rogers, Adam J AU - Rogers AJ AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Haac, Mary Etna R AU - Haac ME AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Cao, Qian AU - Cao Q AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Heffron, C Lynn AU - Heffron CL AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Catanzaro, Nicholas AU - Catanzaro N AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Kenney, Scott P AU - Kenney SP AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Huang, Yao-Wei AU - Huang YW AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. FAU - Opriessnig, Tanja AU - Opriessnig T AD - The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK. FAU - Meng, Xiang-Jin AU - Meng XJ AD - Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA. Electronic address: xjmeng@vt.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141018 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antigens, Viral) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Lectins, C-Type) RN - 0 (Receptors, Cell Surface) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Viral Vaccines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigens, Viral/genetics/*metabolism MH - CD4-Positive T-Lymphocytes/*immunology MH - Cell Adhesion Molecules/genetics/*metabolism MH - Dendritic Cells/*immunology/*metabolism MH - Interferon-gamma/metabolism MH - Lectins, C-Type/genetics/*metabolism MH - Porcine respiratory and reproductive syndrome virus/*immunology MH - Protein Transport MH - Receptors, Cell Surface/genetics/*metabolism MH - Recombinant Fusion Proteins/genetics/metabolism MH - Swine MH - Viral Vaccines/administration & dosage/genetics/*immunology OTO - NOTNLM OT - DC-SIGN OT - Dendritic cell targeting OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Subunit vaccine OT - T cell immunity EDAT- 2014/12/03 06:00 MHDA- 2015/07/24 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/08/15 00:00 [received] PHST- 2014/09/30 00:00 [revised] PHST- 2014/10/06 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/07/24 06:00 [medline] AID - S0264-410X(14)01365-6 [pii] AID - 10.1016/j.vaccine.2014.10.005 [doi] PST - ppublish SO - Vaccine. 2014 Nov 28;32(50):6768-75. doi: 10.1016/j.vaccine.2014.10.005. Epub 2014 Oct 18.