The effect of vaccination with DNA encoding murine T-cell epitopes on the Der p 1 and 2 induced immunoglobulin E synthesis.
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.
Kwon
S S
SS
Division of Allergy and Immunology, Department of Medicine, University of Tennessee School of Medicine, 956 Court Ave., Memphis, TN 38163, USA.
Kim
N
N
Yoo
T J
TJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D039741:Antigens, Dermatophagoides; D004247:DNA / Q000276:immunology*; D000939:Epitopes / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000941:Antigens; D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA