title: Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs.
abstract: Porcine epidemic diarrhea virus (PEDV) first emerged in the United States in 2013 causing high mortality and morbidity in neonatal piglets with immense economic losses to the swine industry. PEDV is an alpha-coronavirus replicating primarily in porcine intestinal cells. PEDV vaccines are available in Asia and Europe, and conditionally-licensed vaccines recently became available in the United States but the efficacies of these vaccines in eliminating PEDV from swine populations are questionable. In this study, the immunogenicity of a subunit vaccine based on the spike protein of PEDV, which was directly targeted to porcine dendritic cells (DCs) expressing Langerin, was assessed. The PEDV S antigen was delivered to the dendritic cells through a single-chain antibody specific to Langerin and the targeted cells were stimulated with cholera toxin adjuvant. This approach, known as "dendritic cell targeting," greatly improved PEDV S antigen-specific T cell interferon-γ responses in the CD4posCD8posT cell compartment in pigs as early as 7days upon transdermal administration. When the vaccine protein was targeted to LangerinposDCs systemically through intramuscular vaccination, it induced higher serum IgG and IgA responses in pigs, though these responses require a booster dose, and the magnitude of T cell responses were lower as compared to transdermal vaccination. We conclude that PEDV spike protein domains targeting Langerin-expressing dendritic cells significantly increased CD4 T cell immune responses in pigs. The results indicate that the immunogenicity of protein subunit vaccines can be greatly enhanced by direct targeting of the vaccine antigens to desirable dendritic cell subsets in pigs.
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Sakthivel
authors: S
authors: Subramaniam
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Dianjun
authors: D
authors: Cao
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Debin
authors: D
authors: Tian
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Qian M
authors: QM
authors: Cao
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Christopher
authors: C
authors: Overend
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Danielle M
authors: DM
authors: Yugo
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Shannon R
authors: SR
authors: Matzinger
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Adam J
authors: AJ
authors: Rogers
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: C Lynn
authors: CL
authors: Heffron
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Nicholas
authors: N
authors: Catanzaro
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors: Scott P
authors: SP
authors: Kenney
authors: The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG Scotland, UK.
authors: Tanja
authors: T
authors: Opriessnig
authors: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Yao-Wei
authors: YW
authors: Huang
authors: Elanco Biological R&D, Eli Lilly and Company, Greenfield, IN 46140, USA.
authors: Geoffrey
authors: G
authors: Labarque
authors: Elanco Biological R&D, Eli Lilly and Company, Greenfield, IN 46140, USA.
authors: Stephen Q
authors: SQ
authors: Wu
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Electronic address: xjmeng@vt.edu.
authors: Xiang-Jin
authors: XJ
authors: Meng
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D002522:Chlorocebus aethiops; D018352:Coronavirus Infections / Q000662:veterinary; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D053485:Porcine epidemic diarrhea virus / Q000276:immunology*; D000072417:Protein Domains / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000276:immunology; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000276:immunology*; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007070:Immunoglobulin A; D057127:Single-Chain Antibodies; D064370:Spike Glycoprotein, Coronavirus; D022223:Vaccines, Subunit; D014765:Viral Vaccines
keywords: Dendritic cell targeting; Porcine Langerin; Porcine epidemic diarrhea virus (PEDV); Subunit vaccine; T cell immunity