Absence of immunoglobulin E synthesis and airway eosinophilia by vaccination with plasmid DNA encoding ProDer p 1.
BACKGROUND
Various studies have shown that immunization with naked DNA encoding allergens induces T helper 1(Th1)-biased non-allergic responses.


OBJECTIVE
To evaluate the polarization of the immune responses induced by vaccinations with plasmid DNA encoding the major mite allergen precursor ProDer p 1.


METHODS
A DNA vaccine was constructed on the basis of a synthetic cDNA encoding ProDer p 1 with optimized codon usage. The immunogenicity of ProDer p 1 DNA in CBA/J mice was compared with that of purified natural Der p 1 or recombinant ProDer p 1 adjuvanted with alum. Vaccinated mice were subsequently exposed to aerosolized house dust mite extracts to provoke airway inflammation. The presence of inflammatory cells was examined in bronchoalveolar lavage (BAL) fluids and allergen-specific T cell reactivity was measured.


RESULTS
Naive mice immunized with ProDer p 1 DNA developed Th1 immune responses characterized by high titres of specific IgG2a antibodies, low titres of specific IgG1 and, remarkably, the absence of anti-ProDer p 1 IgE. No specific responses were observed in animals vaccinated with the blank DNA vector. By contrast, natural Der p 1 or recombinant ProDer p 1 adsorbed to alum induced pronounced Th2 allergic responses with strong specific IgG1 and IgE titres. Spleen cells from DNA ProDer p 1-vaccinated mice secreted high levels of IFN-gamma and low production of IL-5. Conversely, both adjuvanted allergens stimulated typical Th2-type cytokine profile characterized by high and low levels of IL-5 and IFN-gamma, respectively. Whereas BAL eosinophilia was clearly observed in Der p 1-immunized animals, ProDer p 1 DNA as well as ProDer p 1 vaccinations prevented airway eosinophil infiltrations.


CONCLUSIONS
These results suggest that vaccination with DNA encoding ProDer p 1 effectively fails to induce the allergen-induced IgE synthesis and airway cell infiltration. Plasmid DNA encoding ProDer p 1 may provide a novel approach for the treatment of house dust mite allergy.
Jacquet
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Service de Génétique Appliquée, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Gosselies, Belgium. alain.jacquet@ulb.ac.be
Magi
M
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Haumont
M
M
Jurado
M
M
Garcia
L
L
Bollen
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D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics* / Q000276:immunology; D060829:Arthropod Proteins; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003546:Cysteine Endopeptidases; D018076:DNA, Complementary / Q000235:genetics; D004802:Eosinophilia / Q000517:prevention & control*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008808:Mice, Inbred CBA; D008925:Mites / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D018076:DNA, Complementary; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D007073:Immunoglobulin E; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1