Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

Abstract

BACKGROUND
Recent publications indicate that immunization with plasmid DNA encoding allergens might represent a potential approach in allergen-specific immunotherapy.
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.
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-gamma and IL-4 levels were measured by ELISA. Allergen-specific proliferation was determined by incorporation of [(3)H]-thymidine.
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-gamma 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.
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.

Useful keywords (using NLM MeSH Indexing)

Allergens/genetics*

Allergens/immunology*

Animals

Antibody Formation

Antigens, Plant

Base Sequence

Cytokines/biosynthesis

DNA Primers/genetics

DNA, Plant/genetics

Female

Genes, Plant

Humans

Immunization

Lymphocyte Activation

Mice

Mice, Inbred BALB C

Plant Proteins/genetics

Plant Proteins/immunology

Plasmids/genetics

Pollen/genetics*

Pollen/immunology*

Protein Isoforms/genetics

Protein Isoforms/immunology

T-Lymphocytes/immunology

Trees/genetics

Trees/immunology

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