DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response.

Abstract

To establish a new immunotherapy for type I allergic diseases without allergic side effects, we attempted to develop a DNA vaccine encoding both a CD4+ T cell epitope site in a major Japanese cedar pollen allergen (Cry j 2) and an invariant chain (Ii) for the delivery of the epitope peptide into the MHC class II loading pathway. We constructed a plasmid DNA encoding the Ii mutant either by replacement of the core CLIP (class II-associated invariant chain peptide) with a peptide corresponding to the major Cry j 2 CD4+ T cell epitope in BALB/c mice, designated as p247-258 (pCPCJ2), or by fusion of the Ii with p247-258 at the C terminus (pIiCJ2). As expected, repeated inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 induced no antibody response to Cry j 2. In contrast, intramuscular inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 predominantly induced p247-258-specific Th1 cells, resulting in the inhibition of IgE response to subsequent Cry j 2 injections. Our results demonstrated that the plasmid DNA encoding the CD4+ T cell epitope and Ii can induce epitope-specific CD4+ T cell responses in vivo and the potential to regulate type I allergic reaction without allergic side effects.