Article: article from journal or magazin.
Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice.
Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag-coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy.
Adjuvants, Immunologic/administration & dosage, Adjuvants, Immunologic/genetics, Anaphylaxis/immunology, Anaphylaxis/prevention & control, Animals, Antibody Specificity/genetics, Antigens/administration & dosage, Antigens/physiology, Bee Venoms/administration & dosage, Bee Venoms/immunology, CHO Cells, Cells, Cultured, Cricetinae, Cytokines/biosynthesis, Cytokines/secretion, Desensitization, Immunologic/methods, Female, Genetic Vectors/administration & dosage, Genetic Vectors/immunology, Immunoglobulin E/biosynthesis, Immunoglobulin G/biosynthesis, Immunosuppressive Agents/administration & dosage, Lymphocyte Activation/genetics, Mice, Mice, Inbred CBA, Ovalbumin/administration & dosage, Ovalbumin/immunology, Peptide Fragments/administration & dosage, Peptide Fragments/genetics, Phospholipases A/administration & dosage, Phospholipases A/genetics, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, Th1 Cells/immunology, Th1 Cells/metabolism, Transfection, Up-Regulation/genetics, Up-Regulation/immunology, Vaccines, DNA/administration & dosage, Vaccines, DNA/immunology
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