Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy

被引：87

作者：

Chen, Kuan-Wei ^{[1
]}

Blatt, Katharina ^{[2
]}

Thomas, Wayne R. ^{[3
]}

Swoboda, Ines ^{[4
]}

Valent, Peter ^{[2
]}

Valenta, Rudolf ^{[1
,4
]}

Vrtala, Susanne ^{[1
]}

机构：

[1] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, A-1090 Vienna, Austria

[2] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria

[3] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Crawley, Australia

[4] Med Univ Vienna, Christian Doppler Lab Allergy Res, Div Immunopathol, Dept Pathophysiol & Allergy Res, A-1090 Vienna, Austria

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2012年 / 130卷 / 02期

基金：

奥地利科学基金会;

关键词：

Allergy; allergen; specific immunotherapy; recombinant hypoallergen; house dust mite allergy; IGE-BINDING; RECOMBINANT ALLERGENS; DER-P-1; EXPRESSION; REDUCTION; MUTATION; ANTIGEN; FUTURE;

D O I：

10.1016/j.jaci.2012.05.035

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: More than 50% of allergic patients have house dust mite (HDM) allergy. Group 1 and 2 allergens are the major HDM allergens. Objective: We sought to produce and perform preclinical characterization of a recombinant hypoallergenic combination vaccine for specific immunotherapy of HDM allergy. Methods: Synthetic genes coding for 2 hybrid proteins consisting of reassembled Der p 1 and Der p 2 fragments with (recombinant Der p 2 [rDer p 2]/1C) and without (rDer p 2/1S) cysteines were expressed in Escherichia coli and purified to homogeneity by means of affinity chromatography. Protein fold was determined by using circular dichroism analysis, allergenic activity was determined by testing IgE reactivity and using basophil activation assays, and the presence of T-cell epitopes was determined based on lymphoproliferation in allergic patients. Mice and rabbits were immunized to study the molecules' ability to induce an allergic response and whether they induce allergen-specific IgG capable of inhibiting allergic patients' IgE binding to the allergens, respectively. Results: rDer p 2/1C and rDer p 2/1S were expressed in large amounts in E coli as soluble and folded proteins. Because of the lack of disulfide bonds, rDer p 2/1S did not form aggregates and was obtained as a monomeric protein, whereas rDer p 2/1C did form aggregates. Both hypoallergens lacked relevant IgE reactivity and had reduced ability to induce allergic inflammation and allergic responses but induced similar T-cell proliferation as the wild-type allergens. Immunization with the hypoallergens (rDer p 2/1S > rDer p 2/1C) induced IgG antibodies in rabbits that inhibited the IgE reactivity of patients with HDM allergy to Der p 1 and Der p 2. Conclusion: The preclinical characterization indicates that particularly rDer p 2/1S can be used as a safe hypoallergenic molecule for both tolerance and vaccination approaches to treat HDM allergy. (J Allergy Clin Immunol 2012;130:435-43.)

引用

页码：435 / +

页数：13

共 34 条

[21] Reduction in IgE binding to allergen variants generated by site-directed mutagenesis: Contribution of disulfide bonds to the antigenic structure of the major house dust mite allergen Der p 2 [J].