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Division of Immunology and Allergy, R & D Laboratory, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Phospholipase A2 (PLA2) is one of the major
honey bee venom allergens for humans. To assess the long-term
prevention of allergic reactions by DNA vaccination, a
PLA2-CBA/J mouse model was employed using empty or
PLA2 sequence-carrying DNA plasmids. Early skin application
of either DNA construct before (prophylactic approach) or after
(therapeutic approach) sensitization with PLA2/alum led to
reduced PLA2-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-
and
IL-10 secretion and reduced IL-4 production. Recall challenge with
PLA2 boosted IFN- 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.
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