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Biomedical subjects

U Wiedermann

Publications and source records attributed to U Wiedermann.

At least 19 recordsLinked to original sources
PubMed2007

A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.

BACKGROUND: As conventional immunotherapy is less efficacious in patients with allergic multi-sensitivities compared with mono-sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi-sensitization with birch and grass pollen on the basis of mucosal tolerance induction. METHODS: The major birch pollen allergen Bet v 1 served as a scaffold for N- and C-terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli. After purification, physicochemical and immunological characterization the chimer was used for intranasal tolerance induction prior to poly-sensitization with Bet v 1, Phl p 1 and Phl p 5. RESULTS: The immunological characterization revealed that the conformation of Bet v 1 within the chimer was comparable to that of natural as well as recombinant Bet v 1. The chimer was immunogenic in mice for T and B cell responses to the three allergens. Intranasal application of the chimer prior to poly-sensitization significantly suppressed humoral and cellular allergen-specific Th2 responses and prevented development of airway inflammation upon allergen challenge. Moreover, local allergen-specific IgA antibodies were induced by the chimer. The mechanisms of poly-tolerance induction seemed to be mediated by regulatory cytokines, since TGF-beta and IL-10 mRNA in splenocytes were upregulated and tolerance was transferable with these cells. CONCLUSION: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi-sensitivities.

Administration, Intranasal↗
PubMed2006

The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice.

BACKGROUND: Mucosal tolerance induction is suggested as treatment strategy for allergic diseases. Using a murine model of birch pollen (BP) allergy we investigated the long-term efficacy and the underlying mechanisms of mucosal tolerance induction with two structurally different molecules in a prophylactic and in a therapeutic set-up. METHODS: The three-dimensional major BP allergen Bet v 1 or a nonconformational hypoallergenic fragment thereof was intranasally applied before (prophylaxis) or after sensitization (therapy). RESULTS: In the prophylactic application both the Bet v 1 allergen and the fragment prevented allergic sensitization, and this effect lasted for 1 year. In the therapeutic approach established allergic immune responses were also suppressed after treatment with either of the molecules. However, a long-lasting curative effect (6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1 fragment. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of splenocytes revealed that tolerance induction with the Bet v 1 allergen was associated with enhanced expression of transforming growth factor (TGF)-beta, interleukin (IL)-10, and Foxp3 mRNA in CD4+ T cells, whereas treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or IL-10 (therapy) alone. CONCLUSION: From these data we concluded (i) that the mechanisms underlying peripheral tolerance are linked to the conformation of the antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell subsets, and (iii) that the long-term efficacy of immunosuppression is associated with the presence of Foxp3+ T cells.

Administration, Intranasal↗
PubMed2006

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

BACKGROUND: Probiotic lactic acid bacteria (LAB) are able to modulate the host immune system and clinical trials have demonstrated that specific strains have the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the potential of recombinant LAB producing the major birch pollen allergen Bet v 1 for mucosal vaccination against birch pollen allergy. METHODS: Recombinant Bet v 1-producing Lactobacillus plantarum and Lactococcus lactis strains were constructed. Their immunogenicity was compared with purified Bet v 1 by subcutaneous immunization of mice. Intranasal application of the live recombinant strains was performed to test their immunomodulatory potency in a mouse model of birch pollen allergy. RESULTS: Bet v 1 produced by the LAB was recognized by monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients. Systemic immunization with the recombinant strains induced significantly lower IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin (IL)-5 production of splenocytes in vitro, indicating a shift towards non-allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL-5 in lung lavages, was reduced using either Bet v 1-producing or control strains. Allergen-specific secretory IgA responses were enhanced in lungs and intestines after pretreatment with only the Bet v 1-producing strains. CONCLUSIONS: Mucosal vaccination with live recombinant LAB, leading to a shift towards non-allergic immune responses along with enhanced allergen-specific mucosal IgA levels offers a promising approach to prevent systemic and local allergic immune responses.

Administration, Intranasal↗
PubMed2004

Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination.

BACKGROUND: Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food. OBJECTIVE: Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines. METHODS: According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25-32 preferably solvent-exposed amino acids were synthesized. RESULTS: Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation. CONCLUSION: Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.

Allergens↗
PubMed2004

Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy.

The pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (i.p.), subcutaneous (s.c.) or aerosol (a.s.) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After i.p. sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, a.s. sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the s.c. route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.

Aerosols↗
PubMed2003

Induction of mucosal tolerance with recombinant Hev b 1 and recombinant Hev b 3 for prevention of latex allergy in BALB/c mice.

The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure to latex products, such as health-care workers (HCW) and patients with spina bifida (SB). Treatment of latex allergy seems problematic as preventive measures, such as allergen avoidance, are not always possible and conventional immunotherapy with standardized latex extracts is not performed routinely. Thus, the aim of the present study was to establish a mouse model of latex allergy using two major latex allergens for HCWs and SB patients, Hev b 1 and Hev b 3, for sensitization. Prophylactic measures on the basis of mucosal tolerance induction with the recombinant allergens were tested in this model. Female BALB/c mice immunized intraperitoneally with recombinant (r)Hev b 1 or rHev b 3 displayed strong immune responses in vivo and in vitro. Intranasal treatment with rHev b 1 and rHev b 3 prior to sensitization led to reduced allergen-specific IgG1/IgE levels and significantly suppressed allergen-induced basophil degranulation. Moreover, lymphocyte proliferation and cytokine production (IL-4, IL-5, IFN-gamma) in vitro were significantly suppressed after pretreatment with both allergens. Suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-beta, remained unchanged after the intranasal pretreatment, indicating mechanism of anergy rather than active immunosuppression. Taken together, these results suggest that mucosal tolerance induction with recombinant allergens could present a promising prevention strategy against latex allergy.

Allergens↗
PubMed2002

Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice.

BACKGROUND: Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases. OBJECTIVE: The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism. METHODS: A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-gamma) were measured in spleen and lung cell cultures. RESULTS: Mucosal treatment with rBet v 1 (3 x 50 microg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-gamma production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment. CONCLUSION: Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.

Administration, Intranasal↗
PubMed2002

Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help.

BACKGROUND AND OBJECTIVE: In previous studies we have generated mimotopes of Bet v 1, the major birch pollen allergen, by biopannings of phage-display random peptide libraries. In the present study, we analysed the humoral and cellular immune response to Bet v 1-mimotopes. METHODS: The mimotope CFPYCYPSESA, designated Bet mim 1, was used for intraperitoneal immunizations of BALB/c mice in phage-displayed form. For examination of the humoral immune response, enzyme-linked immunosorbent assay (ELISA) experiments were applied. Stimulation capacities were investigated in cultured mouse splenocytes and in humoral Bet v 1-specific T cell clones. RESULTS: We demonstrated that the Bet mim 1-induced murine antibody response against Bet v 1 was predominated by the IgG1 isotype. In these mice only the phage-displayed mimotopes, but neither the allergen nor the synthetic Bet mim 1-mimotopes were able to stimulate proliferation of cultured splenocytes. Using Bet v 1-specific T cell clones of allergic patients, phage-displayed and synthetic mimotopes were unable to stimulate T cell proliferation. Moreover, tolerance induction to Bet v 1 in mice by intranasal administration of Bet mim 1-phages or Bet mim 1-peptide failed. CONCLUSION: Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.

Allergens↗
PubMed2001

Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy.

By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy. We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures. Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.

Allergens↗
PubMed2001

Edible genetically modified microorganisms and plants for improved health.

The development of new strategies for the delivery of vaccine antigens or immune modulators to the mucosal tissue includes innovative approaches such as the use of genetically modified food microorganisms and plants. Even though the 'proof-of-concept' has recently been established for these two systems, key questions mainly related to efficacy and risk of breaking oral tolerance remain to be critically addressed in the immediate future.

Antigens, Bacterial↗
PubMed2001

Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice.

BACKGROUND: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. OBJECTIVE: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. METHODS: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1-74; F II: aa 75-160) prior to aerosol sensitization with birch pollen and Bet v 1. RESULTS: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-gamma, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-beta mRNA levels. CONCLUSION: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

Administration, Intranasal↗
PubMed2000

Rapid production of the major birch pollen allergen Bet v 1 in Nicotiana benthamiana plants and its immunological in vitro and in vivo characterization.

Type I allergies are immunological disorders that afflict a quarter of the world's population. Improved diagnosis of allergic diseases and the formulation of new therapeutic approaches are based on the use of recombinant allergens. We describe here for the first time the application of a rapid plant-based expression system for a plant-derived allergen and its immunological characterization. We expressed our model allergen Bet v 1, the major birch pollen allergen, in the tobacco-related species Nicotiana benthamiana using a tobacco mosaic virus vector. Two weeks postinoculation, plants infected with recombinant viral RNA containing the Bet v 1 coding sequence accumulated the allergen to levels of 200 microg/g leaf material. Total nonpurified protein extracts from plants were used for immunological characterizations. IgE immunoblots and ELISA (enzyme-linked immunoassay) inhibition assays showed comparable IgE binding properties for tobacco recombinant (r) Bet v 1 and natural (n) Bet v 1, suggesting that the B cell epitopes were preserved when the allergen was expressed in N. benthamiana plants. Using a murine model of type I allergy, mice immunized with crude leaf extracts containing Bet v 1 with purified rBet v 1 produced in E. coli or with birch pollen extract generated comparable allergen-specific IgE and IgG1 antibody responses and positive type I skin test reactions. These results demonstrate that nonpurified Bet v 1 overexpressed in N. benthamina has the same immunogenicity as purified Bet v 1 produced in E. coli or nBet v 1. We therefore conclude that this plant expression system offers a viable alternative to fermentation-based production of allergens in bacteria or yeasts. In addition, there may be a broad utility of this system for the development of new and low-cost vaccination strategies against allergy.

Allergens↗
PubMed2000

Different HBs antibody versus lymphoproliferative responses after application of a monovalent (hepatitis B) or combined (hepatitis A + hepatitis B) vaccine.

BACKGROUND: The aim of the study was to evaluate a possible adjuvanticity of simultaneous hepatitis A (HAV) vaccination for the development of HBs-specific antibodies and lymphoproliferative responses in prophylactic immunization with hepatitis B (HBV). METHODS: Thirty-nine volunteers were vaccinated (schedule: 0/1/6 months) either with a bivalent HAV/HBV (18 individuals) or with HBV (recombinant HBs-antigen) vaccine alone (21 individuals). Anti-HBs antibody titers and lymphoproliferative responses as consequence of stimulation of peripheral blood mononuclear cells (PBMC) with HBs were evaluated and compared between the two groups before second vaccination, before and 1 month after booster. RESULTS: Geometric mean titers were higher at all time points in the group treated with the combined vaccine. On the other hand, after the booster injection, HBs-induced stimulation indices in PBMC were higher in the group vaccinated with HBs alone. Neither the difference in antibody titers nor in proliferative responses reached the level of statistical significance. Interestingly, the inverse relation between cellular proliferation and antibodies was significant, indicating that cellular reactivity is not in all cases a useful marker to evaluate the intensity of the induced immunity. CONCLUSIONS: The magnitude of the T-lymphocyte response may eventually not be decisive for the subsequent antibody response. Both vaccination strategies led to a cellular and humoral immune response and resulted in protective levels of HBs-specific antibodies.

Adjuvants, Immunologic↗
PubMed1999

Oligodeoxynucleotides containing CpG motifs modulate the allergic TH2 response of BALB/c mice to Bet v 1, the major birch pollen allergen.

BACKGROUND: The use of adequate adjuvants to modulate the allergic T(H2)-type immune response is a promising concept for future immunotherapy of type I allergy. Bacterial DNA or oligodeoxynucleotides containing CpG motifs (CpG-ODNs) have been demonstrated to foster T(H1)-type immune responses. OBJECTIVE: We investigated the adjuvanticity of CpG-ODNs and their capability to modulate the allergic T(H2) response in a mouse model. METHODS: BALB/c mice were treated with CpG-ODNs and Bet v 1, the major birch pollen allergen, in different experimental setups. Allergen-specific antibody responses, T(H) cytokines, and eosinophilic infiltration of the airways were investigated. RESULTS: Intraperitoneal administration of Bet v 1 together with aluminium hydroxide led to a typical T(H2) response. In contrast, coadminstration of CpG-ODNs with Bet v 1 in aluminium hydroxide resulted in markedly increased T(H1) activities (high IgG2a levels) and subsequently to reduced airway inflammation. The T(H1)-like immune response indicated by these humoral findings was also reflected by decreased IL-5 and increased IFN-gamma levels in cell cultures. CpG-ODNs as sole adjuvants with Bet v 1 did not lead to measureable Ig responses after subcutaneous or intraperitoneal immunizations; after intranasal application, 3 of 10 mice reacted. Nevertheless, a prophylactic effect was obtained with all routes tested; that is, mice treated subsequently with an established aerosol sensitization protocol displayed altered immune responses characterized by drastically elevated levels of Bet v 1-specific IgG2a, indicating a T(H1)/T(H0)-like immunity. Application of CpG-ODNs after aerosol sensitization also induced IgG2a. CONCLUSION: By inducing T(H1)/T(H0)-biased immune responses to allergens, the use of CpG-ODNs as adjuvants may have important impacts for new forms of specific immunotherapy in type I hypersensitivity.

Adjuvants, Immunologic↗
PubMed1999

Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type I allergy.

BACKGROUND: Mucosal (nasal or oral) administration of soluble protein antigens induces a state of antigen-specific immunologic hyporesponsiveness. Several studies have shown that induction of mucosal tolerance can prevent the onset or reduce the severity of certain TH1 -mediated experimental autoimmune diseases. Only a few studies describe similar results for type I allergies, which are caused by excessive TH2 cell activities. OBJECTIVE: We sought to investigate whether mucosal tolerance induction would also be efficient in preventing an allergic type I immune response. METHODS: A murine model of inhalative type I allergy, leading to sensitization to birch pollen and its major allergen Bet v 1 in BALB/c mice, was used. Recombinant Bet v 1 was nasally or orally applied in low doses before sensitization. At the time of death, immediate-type skin tests were performed. Blood was taken, and serum was used for measurement of allergen-specific antibodies. Spleen cell cultures were performed to determine cytokine production (IL-4, IL-5, IL-10, and IFN-gamma), as well as levels of TGF-beta mRNA. RESULTS: Both nasal and oral administration of minimal doses of recombinant Bet v 1 before aerosol sensitization with birch pollen suppressed the allergen-specific antibody production of all isotypes. Consequently, the in vivo type I skin test responses to the allergen were negative in the tolerized, in contrast to the sensitized, group. Moreover, allergen-specific lymphoproliferative responses and cytokine production in vitro (ie, IFN-gamma, IL-4, IL-5, and IL-10) were markedly reduced. In contrast, expression of TGF-beta mRNA was markedly increased in spleen cells from nasally tolerized animals, indicating regulatory mechanisms for tolerance induction. CONCLUSION: We conclude from the present study that nasal, as well as oral, administration of recombinant allergen is an effective way to prevent allergen-specific T- and B-cell responses in a TH2 model.

Administration, Intranasal↗
PubMed1999

Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy.

Recent reports have demonstrated that feeding small amounts of antigen conjugated to the B subunit of cholera toxin (CTB) suppress immune responses in experimental models of certain T(h)1-based autoimmune diseases. We have established a model of aerosol sensitization leading to T(h)2-mediated allergic immune responses in BALB/c mice. In the present study two different antigens, the dietary antigen ovalbumin (OVA) and the inhalant allergen Bet v 1 (the major birch pollen allergen), chemically coupled to recombinant CTB were tested for their potential to influence T(h)2-like immune responses. Intranasal administration of OVA-CTB prior to sensitization with OVA led to a significant decrease of antigen-specific IgE antibody levels, but a marked increase of OVA-specific IgG2a antibodies as compared to non-pretreated, sensitized animals. Antigen-specific lympho-proliferative responses in vitro were reduced by 65% in the pretreated group; IL-5 and IL-4 production were decreased in responder cells of lungs and spleens of nasally pretreated mice. In contrast, mucosal administration of rBet v 1-CTB conjugates prior to sensitization led to an up-regulation of allergen-specific IgE, IgG1 and IgG2a, increased in vitro lympho-proliferative responses as well as augmented production of IL-5, IL-4, IL-10 and IFN-gamma. Intranasal administration prior to sensitization of unconjugated allergens showed also contrasting effects: OVA could not significantly influence antigen-specific antibody or cytokine production, whereas intranasal pretreatment with unconjugated Bet v 1 suppressed allergen-specific immune responses in vivo and in vitro. These results demonstrated that the two antigens-in conjugated as in unconjugated form-had different effects on the T(h)2 immune responses. We therefore conclude that the tolerogenic or immunogenic properties of CTB-and probably also other antigen-delivery systems-strongly depend on the nature of the coupled antigen-allergen.

Administration, Intranasal↗
PubMed1999

Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy.

Recent reports have demonstrated that feeding small amounts of antigen conjugated to the B subunit of cholera toxin (CTB) suppress immune responses in experimental models of certain Th1-based autoimmune diseases. We have established a model of aerosol sensitization leading to Th2-mediated allergic immune responses in BALB/c mice. In the present study two different antigens, the dietary antigen ovalbumin (OVA) and the inhalant allergen Bet v 1 (the major birch pollen allergen), chemically coupled to recombinant CTB were tested for their potential to influence Th2-like immune responses. Intranasal administration of OVA-CTB prior to sensitization with OVA led to a significant decrease of antigen-specific IgE antibody levels, but a marked increase of OVA-specific IgG2a antibodies as compared to non-pretreated, sensitized animals. Antigen-specific lympho-proliferative responses in vitro were reduced by 65% in the pretreated group; IL-5 and IL-4, but not IFN-gamma, production were markedly decreased in responder cells of lungs and spleens of nasally pretreated mice. In contrast, mucosal administration of rBet v 1-CTB conjugates prior to sensitization led to an up-regulation of allergen-specific IgE, IgG1 and IgG2a, increased in vitro lympho-proliferative responses as well as augmented production of IL-5, IL-4, IL-10 and IFN-gamma. Intranasal administration prior to sensitization of unconjugated allergens showed also contrasting effects: OVA could not significantly influence antigen-specific antibody or cytokine production, whereas intranasal pretreatment with unconjugated Bet v 1 suppressed allergen-specific immune responses in vivo and in vitro. These results demonstrated that the two antigens--in conjugated as in unconjugated form--had different effects on the Th2 immune responses. We therefore conclude that the tolerogenic or immunogenic properties of CTB--and probably also other antigen-delivery systems--strongly depend on the nature of the coupled antigen-allergen.

Adjuvants, Immunologic↗