Prevention of long-term IgE antibody production by gene gun-mediated DNA vaccination.
BACKGROUND
Vaccination with allergen-encoding DNA represents a promising approach for the treatment of allergic diseases.


OBJECTIVE
In a mouse model of type I allergy, we analyzed the ability of biolistic transfection to inhibit antigen-specific IgE production and to modulate TH2 responses.


METHODS
BALB/c mice were vaccinated by means of gene gun-mediated DNA immunization with plasmid vector pCMV-betaGal, encoding beta-galactosidase as a model allergen. Subsequently, mice were immunized by means of repeated intraperitoneal injection of beta-galactosidase adsorbed to the adjuvant aluminum hydroxide. Development of IgE, IgG1, and IgG2a antibody titers during the course of immunization was followed, and anaphylactic potential of sera was determined by using RBL-2H3 degranulation assay. Spleen cells of vaccinated mice and unvaccinated control animals were stimulated in vitro to analyze cytokine production and induction of CD8 + effector T cells.


RESULTS
Gene gun-mediated DNA immunization with pCMV-betaGal very efficiently prevented IgE antibody production on a long-term basis. Concomitantly, IgG1 antibody levels in vaccinated mice were strongly reduced, whereas IgG2a antibody production was increased. Analysis of cytokine profiles indicated immune deviation from a TH2-biased response in control mice toward a mixed TH1/TH2 response in vaccinated mice. In addition, substantial numbers of IFN-gamma-producing CD8 + effector T cells were found in vaccinated mice.


CONCLUSIONS
Gene gun-mediated DNA vaccination prevents the induction of long-lasting IgE antibody production.
Ludwig-Portugall
Isis
I
Clinical Research Unit of Allergology, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Montermann
Evelyn
E
Kremer
Andrea
A
Reske-Kunz
Angelika B
AB
Sudowe
Stephan
S
D000818:Animals; D019470:Biolistics / Q000379:methods*; D003587:Cytomegalovirus / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D006967:Hypersensitivity / Q000628:therapy*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*; D001616:beta-Galactosidase / Q000276:immunology
D019444:Vaccines, DNA; D007073:Immunoglobulin E; D001616:beta-Galactosidase