Vaccination with the recombinant allergen ProDer p 1 complexed with the cationic lipid DiC14-amidine prevents allergic responses to house dust mite.
The present study evaluated the prophylactic potential of ProDer p 1, the recombinant precursor form of the major mite allergen Der p 1, combined with the cationic lipid diC14-amidine in a murine model of house dust mite allergy. Naive mice vaccinated with the amidine/allergen complex developed a Th1-biased immune response characterized by the absence of specific IgE, the production of specific IgG2a, and the presence of IFN-gamma in splenocyte cultures. In contrast, ProDer p 1 adjuvanted with alum induced typical strictly Th2-biased allergic responses with strong IgG1 and IgE titers and IL-5 secretion. Removal of negatively charged sialic acids in ProDer p 1 or increasing the ionic strength reduced the binding of ProDer p 1 to the cationic liposomes and resulted in a decrease of the allergen immunogenicity, suggesting that complexation is required for triggering an optimal immune response. Finally, prophylactic vaccination with ProDer p 1-diC14-amidine reduced drastically the production of specific IgE and airway eosinophilia following subsequent immunization with Der p 1-alum and challenge with aerosolized house dust mite extracts. In conclusion, recombinant ProDer p 1 complexed with diC14-amidine could represent an efficient prophylactic vaccine against house dust mite allergy.
Jacquet
Alain
A
Service de Génétique Appliquée, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet, 12, B-6041 Gosselies, Belgium. alain.jacquet@ulb.ac.be
Vanderschrick
Jean-François
JF
Vandenbranden
Michel
M
Elouahabi
Abdelatif
A
Magi
Mauro
M
Garcia
Lida
L
Ruysschaert
Jean-Marie
JM
D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000578:Amidines / Q000737:chemistry / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000737:chemistry / Q000276:immunology*; D060829:Arthropod Proteins; D002412:Cations / Q000737:chemistry; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D014612:Vaccines
D000485:Allergens; D000578:Amidines; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D002412:Cations; D007074:Immunoglobulin G; D008055:Lipids; C089665:N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine; C504325:ProDer p 1 allergen, Dermatophagoides pteronyssinus; D011498:Protein Precursors; D011994:Recombinant Proteins; D014612:Vaccines; D007073:Immunoglobulin E; D007371:Interferon-gamma