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Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs

Subramaniam, Sakthivel, Cao, Dianjun, Tian, Debin, Cao, Qian M., Overend, Christopher, Yugo, Danielle M., Matzinger, Shannon R., Rogers, Adam J., Heffron, C. Lynn, Catanzaro, Nicholas, Kenney, Scott P., Opriessnig, Tanja, Huang, Yao-Wei, Labarque, Geoffrey, Wu, Stephen Q., Meng, Xiang-Jin
Virus research 2017 v.227 pp. 212-219
CD4-positive T-lymphocytes, Porcine epidemic diarrhea virus, adjuvants, antibodies, antigens, blood serum, cholera toxin, dendritic cells, immune response, immunoglobulin A, immunoglobulin G, interferon-gamma, intestines, morbidity, mortality, piglets, pork industry, protein subunits, subunit vaccines, vaccination
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 7days 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.