CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice

Antigen-specific IgE plays an important role in the pathogenesisof allergic disorders. Immunostimulatory CpG motifs (CpG) inbacterial DNA or synthesized oligodeoxynucleotides (ODN) aregaining recognition as potential immunomodulators for switchingon protectiveT_h1-mediated immunity and preventing or potentiallyinhibiting T_h2-dependent allergic responses. To date, allergicmodels used in CpG ODN studies have been established by immunizationof mice with allergen in the presence of adjuvant. This, inaddition to failure to assess specific IgE production in mostof the studies, has limited understanding of the role of CpGODN vaccination in allergic responses. Here, we examine theeffects of synthesized CpG ODN on both developing and ongoingIgE responses in mice sensitized using a recombinant mosquitosalivary antigen (rAed a 2) without adjuvant. Pretreatment ofmice with CpG ODN mixed with rAed a 2 successfully inhibitedsubsequent induction of serum rAed a 2-specific IgE (but notIgG1) and antigen-induced IL-4 and IL-5 production in spleencells. This was associated with an increase of serum IgG2a andIL-12, and increased IFN- and IL-12 production by spleen cells.In this model, however, co-administration of CpG ODN with rAeda 2 to presensitized mice failed to down-regulate ongoing IgEresponses despite significant up-regulation of serum IL-12 andspecific IgG2a. Strikingly, a transient skin delayed-type hypersensitivityreaction occurred in CpG ODN-treated mice. These observationsprovide a new insight into the potential therapeutic applicationof CpG ODN to allergic disorders.