Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy

Background: Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. Methods: Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients’ sera using the CAP system and direct ELISA experiments. Results: Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. Conclusions: The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts.

Section: Discussionmentioning

confidence: 99%

Depigmented and Polymerised House Dust Mite Allergoid: Allergen Content, Induction of IgG4 and Clinical Response

Gallego

Iraola

Himly

et al. 2010

“…However, reduced allergenicity (the key rationale behind the allergoid concept) is not always fulfilled. In fact, Lund et al [24] compared 4 different allergoid preparations with a native allergen, revealing that 1 even displayed greater allergenicity than the unmodified allergen. The potential to induce immediate allergic responses therefore needs to be tested for each allergoid on an individual basis to prove reduced allergenicity in comparison to the native extract.…”

Section: Discussionmentioning

confidence: 99%

The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent

Worm

Ernst²,

Kraller³

et al. 2017

Background: The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified. Methods: Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i.e., TLR4 ligand (extract A*), and native allergen (extract B). Antigen-specific responses after the in vitro stimulation of blood cells with the extracts were assessed by studying costimulatory receptors on the B cell surface by flow cytometry, cytokine responses by ELISA, and CD63 and CD203c upregulation (basophil activation test) in allergic versus nonallergic subjects. Results: HLA-DR selectively increased upon allergen or allergoid treatment in the allergic group only. The extract types elicited similar cytokine responses, with IL-6 and IL-10 production detected only in certain atopic subjects. The allergoids revealed a strong reduction (100- to <10,000-fold) in basophil activation versus native allergen. Reactivity was undetectable in the basophils from nonallergic subjects. Conclusion: The allergenicity of the allergoid employed was sharply reduced when compared to the native allergen, while its immunogenicity was largely retained, especially in the presence of MPL. We also provide further evidence that allergic and nonallergic individuals show preexisting differences in their immune repertoires.

“…The safety profiles observed for allergoids may be related to the increased vaccine concentrations and quick updosing schedules used for allergoids. On the other hand, they may also be explained by the high degree of patient to patient variation observed for allergoids in basophil activation tests [13] and the variable allergenicity that we described previously for different nonstandardized commercially available allergoid products [24]. In addition to this, the IgE inhibition curves investigated previously indicated that the epitope composition of the birch allergoid differs from that of the birch extract, which underscores that the clinical effects of allergoids and allergen extracts each have to be documented in specific studies [24].…”

Section: Discussionmentioning

confidence: 99%

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

Würtzen

Lund

et al. 2007

Background: In Europe, specific immunotherapy is currently conducted with vaccines containing allergen preparations based on intact extracts. In addition to this, chemically modified allergen extracts (allergoids) are used for specific allergy treatment. Reduced allergenicity and thereby reduced risk of side effects in combination with retained ability to activate T cells and induce protective allergen-specific antibody responses has been claimed for allergoids. In the current study, we compared intact allergen extracts and allergoids with respect to allergenicity and immunogenicity. Methods: The immunological response to birch allergen extract, alum-adsorbed extract, birch allergoid and alum-adsorbed allergoid was investigated in vitro in human basophil histamine release assay and by stimulation of human allergen-specific T cell lines. In vivo, Bet v 1-specific IgG titers in mice were determined after repetitive immunizations. Results: In all patients tested (n = 8), allergoid stimulations led to reduced histamine release compared to the intact allergen extract. However, the allergoid preparations were not recognized by Bet v 1-specific T cell lines (n = 7), which responded strongly to the intact allergen extract. Mouse immunizations showed a clearly reduced IgG induction by allergoids and a strongly potentiating effect of the alum adjuvant. Optimal IgG titers were obtained after 3 immunizations with intact allergen extracts, while 5 immunizations were needed to obtain maximal response to the allergoid. Conclusion: The reduced histamine release observed for allergoid preparations may be at the expense of immunological efficacy because the chemical modifications lead to a clear reduction in T cell activation and the ability to induce allergen-specific IgG antibody responses.