Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines.
BACKGROUND
Allergic diseases have become a major public health problem in developed countries; yet, no reliable, safe and consistently effective treatment is available. DNA immunization has been shown to prevent and balance established allergic responses, however, the high dose of conventional DNA vaccines necessary for the induction of anti-allergic reactions and their poor immunogenicity in primates require the development of new allergy DNA vaccines. We evaluated protective and therapeutic effects of a Semliki-Forest Virus replicase-based vs a conventional DNA vaccine in BALB/c mice using the model allergen beta-galactosidase.


METHODS
Immunoglobulin (Ig)E suppression was determined by a basophil release assay as an in vitro correlate for allergen-specific crosslinking capacity of IgE reflecting the in vivo situation in an allergic individual. Th1 memory responses were measured by cytokine detection via enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT).


RESULTS
Nanogram amounts of a replicase-based vector triggered a Th1 response comparable with that achieved with the injection of 20,000-times more copies of a conventional DNA plasmid, and induced IgE suppression in both a protective and a therapeutic setting.


CONCLUSIONS
Replicase-based DNA vaccines fulfill the stringent criteria for an allergy DNA vaccine, i.e. low dose, strong Th1 immunogenicity and memory, lack of 'therapy-induced' IgE production and anaphylactic side effects. Moreover, by triggering apoptosis in transfected cells, their unique 'immunize and disappear' feature minimizes the hypothetical risks of genomic integration or induction of autoimmunity.
Scheiblhofer
S
S
Division of Allergy and Immunology, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Gabler
M
M
Leitner
W W
WW
Bauer
R
R
Zoegg
T
T
Ferreira
F
F
Thalhamer
J
J
Weiss
R
R
D000485:Allergens / Q000276:immunology; D000818:Animals; D001491:Basophils / Q000276:immunology; D045744:Cell Line, Tumor; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology; D005260:Female; D006969:Hypersensitivity, Immediate / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051381:Rats; D012093:Replicon; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA; D001616:beta-Galactosidase / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D019444:Vaccines, DNA; D007371:Interferon-gamma; D001616:beta-Galactosidase