Design of protective and therapeutic DNA vaccines for the treatment of allergic diseases.

Abstract

The DNA vaccine revolution has opened a vast scope of novel approaches for protective and therapeutic treatments of type I allergy. This review gives an overview on the current status of allergy DNA vaccines and presents advances in the design of vaccine constructs. An immense number of concurring studies have proven the stimulation of Th1 cells and the induction of a balanced Th1/Th2 cytokine milieu as the fundamental mechanisms underlying the anti-allergic effects of DNA vaccines. Basic vaccine formulations thus can be optimized by improving the cellular immunogenicity via co-administration of cytokines, co-expression or co-application of immunostimulatory DNA sequences or adapting the codon usage. The latter is a frequent and major reason for impaired vaccine expression (e.g. translation of plant allergen genes in mammal cells). Because of unwanted side effects during conventional specific immunotherapy with allergen extracts, safety is increasingly demanded for both, protein and DNA vaccines for allergy treatment. We discuss the creation of hypoallergenic DNA vaccines based on deliberate allergen gene fragmentation, the use of mutations and the routine production of hypoallergenic DNA vaccines by forced ubiquitination. Furthermore, allergen-expressing DNA replicon vaccines are introduced, which enable a drastic reduction of the vaccine dose without loss of anti-allergic efficacy. Finally, the development of DNA multi vaccines and fusion vaccines for protective and therapeutic applications against certain groups of allergens is addressed.