Genetic immunisation with bovine β-lactoglobulin cDNA induces a preventive and persistent inhibition of specific anti-BLG IgE response in mice

被引:39
作者
Adel-Patient, K
Creminon, C
Boquet, D
Wal, JM
Chatel, JM
机构
[1] CEA Saclay, Lab Inra Immunoallergie Alimentaire, Serv Pharmcol & Immunol, F-91191 Gif Sur Yvette, France
[2] CEA Saclay, Lab Etud Radioimmunol, DSV, Serv Pharamacol & Immunol, F-91191 Gif Sur Yvette, France
关键词
allergy; DNA immunisation; Th1/Th2; beta-lactoglobulin; bovine;
D O I
10.1159/000049495
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background. Various studies have shown that DNA immunisation with gene allergen induces a non-allergic response. Methods: We applied this new type of vaccination to bovine beta -lactoglobulin (BLG), a major cow's milk allergen, using a plasmid that allows the production of a partially secreted protein. Specific antibodies and cytokines were quantified in different immunisation protocols. Results: The primary response in mice immunised with BLG-encoding plasmid (pBLG) is of the Th1 type. Restricted recognition of a native form of BLG in pBLG mice contrasted with a broader range of recognition in BLG-in-alum-immunised mice, notwithstanding the fact that alum favours the presentation of a native form of the antigen. We also demonstrated an inhibitory effect of pDNA immunisation on the Th2 response induced by a subsequent immunisation using BLG adsorbed on alum. However, this preventive effect is highly dependent on the time of pre-administration of the pBLG, with an optimal effect when pDNA immunisation occurred at least 21 days before protein administration. This preventive effect resulted concomitantly in the inhibition of BLG-specific IgE, in the induction of specific IgG2a, and in the decrease of the specific IgG1/IgG2 ratio. It is accompanied by an increase in IFN gamma and IL-10 secretion. Moreover, the preventive effect was shown to be persistent even after a booster immunisation with alum-adsorbed BLG. The Th1 orientation of the response is very likely due to the presentation of the protein in theTh1 environment due to plasmid immunostimulatory sequences, as intramuscular injection of BLG itself leads to a weak Th2 response and had no preventive effect on a subsequent sensitisation. Conclusion: This study further demonstrates the potential use of DNA immunisation for prevention of IgE response, but the window of action seems to be very restricted if we are to inhibit an established Th2 response efficiently. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:59 / 67
页数:9
相关论文
共 49 条
[1]   Evaluation of a high IgE-responder mouse model of allergy to bovine β-lactoglobulin (BLG):: development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a in BLG-sensitized mice [J].
Adel-Patient, K ;
Créminon, C ;
Bernard, H ;
Clément, G ;
Négroni, L ;
Frobert, Y ;
Grassi, J ;
Wal, JM ;
Chatel, JM .
JOURNAL OF IMMUNOLOGICAL METHODS, 2000, 235 (1-2) :21-32
[2]   COMPLETE SEQUENCE OF THE BOVINE BETA-LACTOGLOBULIN CDNA [J].
ALEXANDER, LJ ;
HAYES, G ;
PEARSE, MJ ;
BEATTIE, CW ;
STEWART, AF ;
WILLIS, IM ;
MACKINLAY, AG .
NUCLEIC ACIDS RESEARCH, 1989, 17 (16) :6739-6739
[3]  
[Anonymous], 1998, European Commission - Council Directive 98/83/EC. L330
[4]   EXPRESSION OF RECOMBINANT BOVINE BETA-LACTOGLOBULIN IN ESCHERICHIA-COLI [J].
BATT, CA ;
RABSON, LD ;
WONG, DWS ;
KINSELLA, JE .
AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 1990, 54 (04) :949-955
[5]   Influence of cellular location of expressed antigen on the efficacy of DNA vaccination: cytotoxic T lymphocyte and antibody responses are suboptimal when antigen is cytoplasmic after intramuscular DNA immunization [J].
Boyle, JS ;
Koniaras, C ;
Lew, AM .
INTERNATIONAL IMMUNOLOGY, 1997, 9 (12) :1897-1906
[6]  
Broide D, 1998, J IMMUNOL, V161, P7054
[7]   Oligonucleotide adjuvants for T helper 1 (Th1)-specific vaccination [J].
Carson, DA ;
Raz, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1621-1622
[8]   Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12 [J].
Chace, JH ;
Hooker, NA ;
Mildenstein, KL ;
Krieg, AM ;
Cowdery, JS .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1997, 84 (02) :185-193
[9]   Expression of a lipocalin in prokaryote and eukaryote cells:: Quantification and structural characterization of recombinant bovine β-lactoglobulin [J].
Chatel, JM ;
Adel-Patient, K ;
Créminon, C ;
Wal, JM .
PROTEIN EXPRESSION AND PURIFICATION, 1999, 16 (01) :70-75
[10]  
Chun S, 1999, J IMMUNOL, V163, P2393