Isoforms of the Major Allergen of Birch Pollen Induce Different Immune Responses after Genetic Immunization

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Abstract
Background: Recent publications indicate that immunization with plasmid DNA encoding allergens might represent a potential approach in allergen–specific immunotherapy. Objective: In the present study we have compared the immune responses induced by plasmid DNA encoding for two isoforms of Bet v 1, the major allergen of birch pollen. Methods: BALB/c mice were injected intradermally with plasmid DNA encoding for the genes of Bet v 1a (pCMV–Beta) and Bet v 1d (pCMV–Betd). In addition, the effect of immunostimulatory DNA sequences was investigated by appending and/or coinjecting CpG motifs. Antibody responses and IFN–γ and IL–4 levels were measured by ELISA. Allergen–specific proliferation was determined by incorporation of [3H]–thymidine. Results: The two isoforms induced a similar humoral response. The lack of any IgE production and the ratio of IgG1 to IgG2a clearly indicated a Th–1–type response. The antisera against both isoforms were highly cross–reactive, which was supported by the energy plot indicating similar folding of the two protein isoforms. However, determination of IFN–γ and IL–4 in the serum elicited a strikingly different cytokine profile during the course of the immune response. In contrast to pCMV–Beta, pCMV–Betd caused no significant allergen–specific proliferation and induced only marginal levels of the key cytokines. Conclusions: Based on the assumption that the induction of a strong Th–1 type response is a prerequisite for successful treatment of allergy, our results favor the use of isoform Bet v 1a in combination with CpG motifs for a novel type of allergen immunotherapy based on plasmid DNA immunization. Additionally, the data also confirm the assumption that the antigen itself can have a marked influence on the immune response after genetic immunization.

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