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 f or 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 constr uct before (prophylactic approach) or after (therapeutic approach) sensitiz ation with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers a t 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, bo osted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiesce nt memory Th1 lymphocytes. Rice from the prophylactic groups were fully pro tected against anaphylaxis, whereas 65% of the animals recovered in the the rapeutic groups. Th1-polarized immune responses were also active in mice va ccinated with an empty plasmid 32 wk before sensitization with another Ag ( OVA). This is the first demonstration that the Ag-coding sequence in DNA va ccine 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-te rm treatment of allergy.