Chemical Modification of Birch Allergen Extract Leads to a Reduction in Allergenicity as well as Immunogenicity

Würtzen, Peter Adler; Lund, G.; Lund, L.; Lund, Kaare; Henmar, H.

doi:10.1016/j.jaci.2005.12.1287

Cited by 15 publications

(25 citation statements)

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“…Despite the lower allergen and alum content of Intact‐Allergen‐3, this vaccine induces T cell activation at a higher level than that observed with three of the four allergoid products. The low level of sIgG that was observed in mice immunized with Intact‐Allergen‐3 may be explained by the low content of alum, because alum is known to influence this parameter strongly in mice [25,26]. Thus, among the three intact allergen vaccines a clear dose–response relationship was seen when taking both the major allergen amount and alum content into consideration.…”

Section: Discussionmentioning

confidence: 98%

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Henmar

Lund

et al. 2008

Clinical and Experimental Immunology

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SummaryDifferent vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

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Section: Discussionmentioning

confidence: 98%

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Henmar

Lund

et al. 2008

Clinical and Experimental Immunology

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“…for formaldehyde and Lee et al 22 . for glutaraldehyde, as previously described 19 . First, allergen extracts were filtered through a 0·45‐μm filter.…”

Section: Methodsmentioning

confidence: 99%

“…Formaldehyde and glutaraldehyde react with primary amino groups in the polypeptide chain of the allergen leading to intramolecular and intermolecular cross‐linked high‐molecular‐weight allergen polymers; in this way conformational IgE epitopes should be destroyed while the linear T‐cell epitopes remain unaffected 12–15 . However, some publications have demonstrated that allergoids also display a reduced T‐cell stimulatory capacity 16–19 . Additionally, the stimulation of T cells by the allergoid seems to be dependent on the type of antigen‐presenting cell: whereas dendritic cells (DC) and macrophages are highly effective cells for the presentation of allergoids, peripheral blood mononuclear cells (PBMC) and B cells are less effective 17,20 .…”

Section: Introductionmentioning

confidence: 99%

Reduced in vitro T‐cell responses induced by glutaraldehyde‐modified allergen extracts are caused mainly by retarded internalization of dendritic cells

et al. 2012

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SummaryAlthough allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4 + T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-c production by, CD4 + T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4 + T cells stimulated with intact allergen-treated or formaldehyde allergoidtreated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/ aggregation and diminished uptake by DC.

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“…The FITC-labeled allergen extracts were added to the apical side of polarized AECs with MDDCs attached to the AEC basal side. Bet v 1-specific T cells were generated as previously described from allergic patients and stored in liquid nitrogen (25). The pre-generated Bet v 1 T cells and the subsequently generated MDDCs were derived from the same donor (autologous).…”

Section: Allergen Uptake and Allergen-specific Stimulation Of Autologmentioning

confidence: 99%

Effect of Polarization on Airway Epithelial Conditioning of Monocyte-Derived Dendritic Cells

Chhoden

Arge

Vorup-Jensen

et al. 2015

Am J Respir Cell Mol Biol

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Airway epithelial cells (AECs) form polarized barriers that interact with inhaled allergens and are involved in immune homeostasis. We examined how monocyte-derived dendritic cells (MDDCs) are affected by contact with the airway epithelium. In traditional setups, bronchial epithelial cell lines were allowed to polarize on filter inserts, and MDDCs were allowed to adhere to the epithelial basal side. In an optimized setup, the cell application was reversed, and the culture conditions were modified to preserve cellular polarization and integrity. These two parameters were crucial for the MDDCs' immunoregulatory properties; thus, previous observations obtained using traditional setups should be considered with caution. Using the optimized setup, AEC conditioning of MDDCs led to increased expression of programmed death 1 ligand 1, immunoglobulin-like transcript 3, CD40, CD80, and CD23. This increased expression was accompanied by decreased secretion of monocyte chemotactic protein 1 and eotaxin and donor-variable effects on IL-12 and IL-10 secretion. Conditioning varied between maturation states and depended partly on direct contact between AECs and MDDCs. The setup allowed MDDCs on the basal side of the epithelium to sample allergens administered to the apical side. Allergen uptake depended on polarization and the nature of the allergen. AEC conditioning led to decreased birch allergen-specific proliferation of autologous T cells and a trend toward decreased secretion of the Th2-specific cytokines IL-5 and IL-13. In conclusion, we determined that AEC conditioning favoring cellular integrity leads to a tolerogenic MDDC phenotype, which is likely to be important in regulating immune responses against commonly inhaled allergens.

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Chemical Modification of Birch Allergen Extract Leads to a Reduction in Allergenicity as well as Immunogenicity

Cited by 15 publications

References 0 publications

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Reduced in vitro T‐cell responses induced by glutaraldehyde‐modified allergen extracts are caused mainly by retarded internalization of dendritic cells

Effect of Polarization on Airway Epithelial Conditioning of Monocyte-Derived Dendritic Cells

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