Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines.

Abstract:

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.

journal_name

Allergy

journal_title

Allergy

authors

Scheiblhofer S,Gabler M,Leitner WW,Bauer R,Zoegg T,Ferreira F,Thalhamer J,Weiss R

doi

10.1111/j.1398-9995.2006.01142.x

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

828-35

issue

7

eissn

0105-4538

issn

1398-9995

pii

ALL1142

journal_volume

61

pub_type

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