Short‐term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T‐cell responses, in patients with allergic rhinitis

Klimek, Ludger; Dormann, D; Jarman, Edward J.; Cromwell, Oliver; Riechelmann, Herbert; Reske-Kunz, A B

doi:10.1046/j.1365-2222.1999.00651.x

Cited by 66 publications

(48 citation statements)

References 41 publications

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“…All these molecules exhibit a decreased binding capacity for IgEs, and are shown following intradermal injection to display a lower reactogenicity and a decreased capacity to release proinflammatory mediators and Th2 cytokines when compared to wild-type rBet v 1 [18]. While this approach should lead in theory to safe vaccines, there is as of today only limited proof of efficacy obtained in small cohorts of patients for nonnative allergens [37]. As a matter of fact, IgE binding might otherwise facilitate allergen capture and presentation by professional antigen-presenting cells such as dendritic cells and activated B lymphocytes, which are known to express both high and low affinity (Fc ε RI and CD23) [38, 39]surface receptors for IgE, respectively.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Wild-Type Recombinant Bet v 1a as a Candidate Vaccine against Birch Pollen Allergy

Batard

Didierlaurent

Chabre

et al. 2005

Int Arch Allergy Immunol

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Background: We describe the production in Escherichia coli as a recombinant protein of clinical grade wild-type Bet v 1a (rBet v 1a), to be used as a candidate vaccine against birch pollen allergy. Methods: This recombinant protein was purified by hydrophobic interaction and ion exchange chromatography and characterized by SDS-PAGE, immunoprint and circular dichroism in parallel with natural Bet v 1 (nBet v 1) purified from a birch pollen extract. We also compared rBet v 1 and nBet v 1 for their capacity to induce histamine release from basophils and to stimulate T lymphocyte proliferation. Results: rBet v 1a appears in SDS-PAGE as an 18-kDa monomeric protein, whereas purified nBet v 1 comprises a mixture of isoforms (resolving as three distinct bands and six spots after 1-dimensional and 2-dimensional electrophoresis, respectively). Both recombinant and natural purified Bet v 1 molecules are recognized by IgE from birch pollen-allergic patients as well as anti-Bet v 1 murine monoclonal antibodies, suggesting that the recombinant protein is correctly folded in a native configuration. Circular dichroism analysis confirmed that the two Bet v 1 molecules exhibit similar 3-dimensional structures, even if rBet v 1a appears more compact and stable in thermodenaturation/renaturation experiments. Both rBet v 1 and nBet v 1 induce the degranulation of sensitized basophils and proliferation of Bet v 1-specific T lymphocytes in a similar manner. Conclusions: On the basis of these structural and biological properties, rBet v 1a is a valid candidate vaccine against birch pollen allergy, currently evaluated in humans.

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Section: Discussionmentioning

confidence: 99%

Characterization of Wild-Type Recombinant Bet v 1a as a Candidate Vaccine against Birch Pollen Allergy

Batard

Didierlaurent

Chabre

et al. 2005

Int Arch Allergy Immunol

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“…A shift of the cytokine profile toward Th1 during treatment with an OVA allergoid was shown in mice (4). In humans effective allergoid therapy was evident by significant reduction of the IL-5 production in nasal secretions accompanied by increased IFN-␥ production (13), indicating the involvement of T cells in this beneficial effect.…”

mentioning

confidence: 96%

T Cell Reactivity with Allergoids: Influence of the Type of APC

Kahlert

Grage-Griebenow

Stüwe

et al. 2000

The Journal of Immunology

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The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

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“…Both, a shift toward Th1, 71,72 as well as an unchanged Th1/Th2-ratio, [73][74][75] was observed. However, cultures of PBMCs do not provide accurate insights into immune responses of affected organs and associated lymphoid tissue.…”

Section: Discussionmentioning

confidence: 91%

“…An increased Th1/Th2 ratio, with mostly unchanged Th2 but increased Th1 cytokines (IL-2, IFN-g and IL-12) was demonstrated in skin biopsy upon intradermal challenge after grass pollen SIT, 76 in mucosal biopsy upon intranasal provocation after pollen SIT, 77 and in nasal biopsies and nasal fluids in response to natural pollen exposure in patients after pollen SIT. 73,75 However, these studies demonstrated the change of whole T cells in the tissues and due to technical problems could not focus on allergen-specific T cell subsets.…”

Section: Discussionmentioning

confidence: 99%