Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs
| Autor: | Scott P. Kenney, Sakthivel Subramaniam, Qian M. Cao, Tanja Opriessnig, Nicholas Catanzaro, Yao-Wei Huang, Debin Tian, Geoffrey Gregory Labarque, Xiang-Jin Meng, Christopher Overend, Adam J. Rogers, Danielle M. Yugo, Dianjun Cao, Wu Stephen, C. Lynn Heffron, Shannon R. Matzinger |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cancer Research Swine Antibodies Viral Antibody Specificity T-Lymphocyte Subsets Chlorocebus aethiops Intestinal Mucosa Antigens Viral Swine Diseases biology integumentary system T cell immunity Immunogenicity Infectious Diseases medicine.anatomical_structure Spike Glycoprotein Coronavirus Vaccines Subunit Coronavirus Infections Langerin T cell CHO Cells Subunit vaccine Article 03 medical and health sciences Immune system Cricetulus Antigen Protein Domains Virology medicine Porcine epidemic diarrhea virus (PEDV) Animals Vero Cells Porcine epidemic diarrhea virus Dendritic cell targeting Viral Vaccines Dendritic cell Dendritic Cells biology.organism_classification Antibodies Neutralizing Immunoglobulin A 030104 developmental biology Porcine Langerin Immunology biology.protein Immunization CD8 Single-Chain Antibodies |
| Zdroj: | Virus Research Subramaniam, S, Cao, D, Tian, D, Cao, Q M, Overend, C, Yugo, D M, Matzinger, S R, Rogers, A J, Heffron, C L, Catanzaro, N, Kenney, S P, Opriessnig, T, Huang, Y-W, Labarque, G, Wu, S Q & Meng, X-J 2017, ' Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs ', Virus Research, vol. 227, pp. 212-219 . https://doi.org/10.1016/j.virusres.2016.10.007 |
| ISSN: | 1872-7492 |
| Popis: | Highlights • Targeting PEDV spike protein domains to Langerin-expressing dendritic cells through a single chain antibody. • Transdermal Langerin-targeting of PEDV S antigen significantly enhanced CD4 T cell immunity. • Systemic Langerin-targeting of PEDV S antigen significantly augmented serum IgG and IgA responses. 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 CD4posCD8pos T cell compartment in pigs as early as 7 days upon transdermal administration. When the vaccine protein was targeted to Langerinpos DCs 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. |
| Databáze: | OpenAIRE |
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