Development of New Immunotherapies for Japanese Cedar Pollinosis

Abstract

We developed new immunotherapies (peptide and DNA vaccines) for treatment of Japanese cedar pollinosis. In the first place, oral administration of a dominant T cell epitope of a major Japanese cedar allergen (Cry j 2) in mice induced immunologic tolerance in both T-helper (Th) 1 and Th2 cell responses against the whole protein allergen. We found that peptide-based oral immunotherapy has a potential efficacy for treatment of the allergic immune response. Further, we developed a hybrid peptide comprising 7 T cell epitopes for human patients. It is expected that the hybrid peptide will downregulate allergen-specific T cells. We are planning a clinical study with the hybrid peptide in the near future. In the second place, we evaluated the use of DNA immunization by inoculating mice with plasmid DNA encoding a major Japanese cedar allergen (Cry j 1) gene. This DNA vaccination suppressed the IgE and IgG1 responses to subsequent alum-precipitated Cry j 1 injections. These results suggest that the DNA vaccination effectively induced Cry j 1-specific Th1-type immune responses, resulting in inhibition of the IgE responses to Cry j 1. Further, we developed DNA vaccine encoding both T cell epitope in Cry j 2 and invariant chain for the delivery of the epitope peptide into major histocompatibility complex (MHC) class II loading pathway. This DNA vaccination also suppressed the IgE responses to subsequent alum-precipitated Cry j 2 injections. DNA vaccine encoding T cell epitope and invariant chain induced epitope-specific T cell responses without allergic side effects.