title: 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.
abstract: 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-γ 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.
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Piñeyro
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Debin
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Overend
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Yugo
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Matzinger
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rogers
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Mary Etna R
authors.initials: ME
authors.lastname: Haac
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: C Lynn
authors.initials: CL
authors.lastname: Heffron
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Catanzaro
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Kenney
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
authors.forename: Yao-Wei
authors.initials: YW
authors.lastname: Huang
authors.affiliation: The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
authors.forename: Tanja
authors.initials: T
authors.lastname: Opriessnig
authors.affiliation: 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.
authors.forename: Xiang-Jin
authors.initials: XJ
authors.lastname: Meng
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D007371:Interferon-gamma; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: DC-SIGN; Dendritic cell targeting; Porcine reproductive and respiratory syndrome virus (PRRSV); Subunit vaccine; T cell immunity