Strategies for the development of safe and effective DNA vaccines for allergy treatment.
During the past ten years, a great number of studies have demonstrated that injection of plasmid DNA coding for certain genes results in the induction of humoral and cellular immune responses against the respective gene product. The features of DNA vaccines enable a broad range of applications, including the induction of protective immunity against viral, bacterial, and parasitic infections, and open up new perspectives for the treatment of cancer. Furthermore, based on their Th1-promoting properties, DNA vaccines also turned out to balance Th2-mediated immune reactions, a quality which renders them a promising alternative for immunotherapy against allergy. Their unique immunological properties offer new possibilities for the development of vaccines, which do not cause anaphylactic side effects, a major drawback of specific immunotherapy (SIT). In this review, we present approaches to avoid the translation of native allergenic determinants, thus preventing release of allergy mediators stimulated by crosslinking of pre-existing or vaccine-induced IgE antibodies on mast cells. Three approaches are described, which fulfill these requirements: (i) cutting the allergen gene into overlapping fragments, which lack any antigenic determinant of the native allergen, but display the original repertoire of T cell epitopes, (ii) using hypoallergenic derivatives or (iii) fusing the allergen with ubiquitin, thus fragmenting the antigen and destroying its native structure. The presented experiments demonstrate that DNA vaccines are suitable to balance an allergic response in a protective as well as a therapeutic experimental design, thus demonstrating their potential for allergy treatment. In addition to conventional plasmid DNA vaccines, aspects and perspectives of replicon-based DNA vaccines will be discussed.
Hartl
Arnulf
A
AKH Wien Division of Immopathology, Währinger Gürtel 18-20, A-1090 Wien.
Weiss
Richard
R
Hochreiter
Romana
R
Scheiblhofer
Sandra
S
Bauer
Roman
R
Valenta
Rudolf
R
Ferreira
Fatima
F
Leitner
Wolfgang
W
Thalhamer
Josef
J
D000485:Allergens / Q000276:immunology; D000818:Animals; D004345:Drug Industry; D000939:Epitopes; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D000485:Allergens; D000939:Epitopes; D019444:Vaccines, DNA