Hyposensitization to allergic reaction in rDer f 2-sensitized mice by the intranasal administration of a mutant of rDer f 2, C8/119S.
C8/119S is a mutant of recombinant Der f 2 (rDer f 2), and lacks a disulphide bond possessed by wild-type rDer f 2. In humans and mice, C8/119S has a very weak IgE-binding capacity compared with the wild-type, but possesses a T cell reactivity comparable to that of the wild-type. C8/119S may thus be a safe immunotherapeutic agent for house dust mite allergy. The aim of the present study was to evaluate whether the intranasal administration of C8/119S could suppress an immediate allergic reaction in mice sensitized with wild-type rDer f 2, possessing an allergic activity comparable to native counterparts purified from mite extract. Seven-week-old male A/J mice were immunized with wild-type rDer f 2 four times, and then intranasally administered 0.2-2 microg of wild-type, 0.2-20 microg of C8/119S, or PBS alone, three times a week for 4 weeks. Seven days after the last administration, the mice were examined for an immediate allergic reaction. The animals administered 2 microg of C8/119S (C2.0 group) showed significantly reduced immediate bronchoconstriction provoked by the i.v. injection of 1 and 10 microg of wild-type rDer f 2, compared with the PBS-treated mice. Similar results were obtained when we examined mice 10 weeks after the last administration. The reactions in the other groups given wild-type or C8/119S also tended to decrease in severity in comparison with the animals of the PBS group. The allergic phenotypes of the T cells, B cells, and basophils in the C2.0 group were shifted to that of naive mice without immunization. We conclude that C8/119S has hyposensitizing activities in mice sensitized with wild-type rDer f 2. C8/119S may be useful for immunotherapy of house dust mite allergy.
Bioscience Research and Development Laboratory, Asahi Breweries Ltd, Ibaraki, Japan.
M
M
Yasue
T
T
Yokota
M
M
Fukada
T
T
Takai
M
M
Suko
H
H
Okudaira
Y
Y
Okumura
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D008925:Mites; D016297:Mutagenesis, Site-Directed; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D015850:Interleukin-6; D011994:Recombinant Proteins; D007371:Interferon-gamma