[Prevention of an IgE response to bovine beta-lactoglobulin by gene immunization in mice].
The therapeutic routes for the treatment of allergy have as their objective to prevent or diminish the specific IgE responsible for the appearance of the allergic reaction. This allergic reaction survives in the genetically predisposed subject and results in a dis-equilibrium of the "Th1-Th2 balance" by increasing the Th2 response. This Th2 response induces the production of IgE against environmental antigens, which from that time on become allergens. In this context, use of gene immunisation seems to be very interesting. The immunisation consists of the injection of an expression vector of bacterial origin, containing the cDNA of a protein of interest. Different studies have shown that the injection of such a plasmid into mice initiates a specific immune response of Th1 (IgG2a) type, stopping all further response of the Th2 (IgG1 and IgE) type. This "non-allergic" response is due to the intrinsic properties of the bacterial ADN, notably the presence of sequences of immunostimulants, the adjuvant of the Th1 response. We have sought to show such a preventative effect in the case of a food protein, bovine beta-lactoglobulin (BLG), a major allergen of cow's milk. Firstly, we made a expression plasmid that contained the cDNA of BLG. Intramuscular administration of this plasmid to mice allowed expression of the BLG in the native form at the site of the injection. The primary response induced by this type of immunisation is characterised by a mixed IgG1/IgG2a response and an absence of anti-BLG IgE. In addition, pre-immunisation of the mice with a plasmid that contained the cDNA of BLG prevented all further sensitisation with the protein administered by the intra-peritoneal route in the presence of alum, an adjuvant of the Th2 response. It appeared further that the preventative effect is dependent on the latent time between gene and protein immunisation. Prevention of the anti-BLG IgE response seems to result in an active inhibition by the cytokines such as interferon-gamma and interleukin 10, rather than a reduction in the production of type Th2 cytokines. Use of efficacious non-pathogenic vectors, that may be administered by the digestive route, could envisage a specific protection in the case of severe food allergies.
Adel-Patient
K
K
Laboratoire Inra d'Immuno-Allergie Alimentaire, Bât 136, CEA de Saclay, 91191 Gif-sur-Yvette, France.
Créminon
Ch
Ch
Boquet
D
D
Wal
J M
JM
Chatel
J M
JM
D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007273:Injections, Intramuscular; D016753:Interleukin-10 / Q000378:metabolism; D007782:Lactoglobulins / Q000235:genetics / Q000276:immunology*; D016269:Milk Hypersensitivity / Q000517:prevention & control*; D010957:Plasmids / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D018076:DNA, Complementary; D007074:Immunoglobulin G; D007782:Lactoglobulins; D019444:Vaccines, DNA; D016753:Interleukin-10; D007073:Immunoglobulin E