Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice.
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.
Jilek
S
S
Division of Immunology and Allergy, R & D Laboratory, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Barbey
C
C
Spertini
F
F
Corthésy
B
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D000941:Antigens / Q000008:administration & dosage / Q000502:physiology*; D001514:Bee Venoms / Q000008:administration & dosage / Q000276:immunology*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010741:Phospholipases A / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000941:Antigens; D001514:Bee Venoms; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D019444:Vaccines, DNA; D007073:Immunoglobulin E; D010047:Ovalbumin; D010741:Phospholipases A