S S Kwon1, N Kim, T J Yoo. 1. Division of Allergy and Immunology, Department of Medicine, University of Tennessee School of Medicine, 956 Court Ave., Memphis, TN 38163, USA.
Abstract
BACKGROUND: Immunization with naked plasmid DNA leads to strong and persistent cell-mediated and humoral immune response to plasmid encoded antigen. Vaccination of DNA encoded whole allergen has been tried, but little information is currently available on the efficacy of DNA encoding T-cell epitopes in allergic disease. The purpose of this study was to determine whether the vaccination of naked plasmid DNA encoding only T-cell epitopes suppresses the allergic reaction as effectively as naked DNA encoding whole segments of allergen. METHODS: We immunized mice with a mixed naked plasmid DNA encoding the five classes of murine T-cell epitopes on Der p 1 and Der p 2 three times at weekly intervals via an intramuscular injection of BALB/c mice. Control mice were injected with the pcDNA 3.1 blank vector. After 3 weeks, the mice were actively sensitized twice and allowed to inhale the Der p extracts intranasally six times at weekly intervals. RESULTS: The vaccinated mice showed a significant attenuated induction of Der p-specific immunoglobulin E synthesis compared to controls. In terms of the Der p-specific IgG2a antibody response, the vaccinated mice showed more prominent responses than the control mice group. In addition, analysis of the cytokine profile after Der p stimulation of the lymph-node cells revealed that the level of the mRNA expression of the interferon-gamma gene was higher in the vaccinated mice than in the controls. Histologic studies showed a much reduced infiltration of inflammatory cells in lung tissue of the gene-vaccinated mice in comparison with the controls. CONCLUSIONS: These results suggest that vaccination with DNA encoding T-cell epitopes effectively inhibits allergen-induced IgE synthesis and reduces cell infiltration in lung tissue. Thus, gene therapy using T-cell epitope-encoding DNA presents an ideal way of combating allergic disease in the future.
BACKGROUND: Immunization with naked plasmid DNA leads to strong and persistent cell-mediated and humoral immune response to plasmid encoded antigen. Vaccination of DNA encoded whole allergen has been tried, but little information is currently available on the efficacy of DNA encoding T-cell epitopes in allergic disease. The purpose of this study was to determine whether the vaccination of naked plasmid DNA encoding only T-cell epitopes suppresses the allergic reaction as effectively as naked DNA encoding whole segments of allergen. METHODS: We immunized mice with a mixed naked plasmid DNA encoding the five classes of murine T-cell epitopes on Der p 1 and Der p 2 three times at weekly intervals via an intramuscular injection of BALB/c mice. Control mice were injected with the pcDNA 3.1 blank vector. After 3 weeks, the mice were actively sensitized twice and allowed to inhale the Der p extracts intranasally six times at weekly intervals. RESULTS: The vaccinated mice showed a significant attenuated induction of Der p-specific immunoglobulin E synthesis compared to controls. In terms of the Der p-specific IgG2a antibody response, the vaccinated mice showed more prominent responses than the control mice group. In addition, analysis of the cytokine profile after Der p stimulation of the lymph-node cells revealed that the level of the mRNA expression of the interferon-gamma gene was higher in the vaccinated mice than in the controls. Histologic studies showed a much reduced infiltration of inflammatory cells in lung tissue of the gene-vaccinated mice in comparison with the controls. CONCLUSIONS: These results suggest that vaccination with DNA encoding T-cell epitopes effectively inhibits allergen-induced IgE synthesis and reduces cell infiltration in lung tissue. Thus, gene therapy using T-cell epitope-encoding DNA presents an ideal way of combating allergic disease in the future.