Comparative Study of Tolerance between Unmodified and High Doses of Chemically Modified Allergen Vaccines of <i>Dermatophagoides pteronyssinus</i>

Abstract

Background: The physiochemical modification of allergens to reduce allergenicity, while retaining immunogenicity, provides a chance for the administration of higher doses of immunotherapy, with a decreased risk of systemic reactions. Objective: To evaluate the safety of doses of depigmented glutaraldehyde-polymerized vaccine of Dermatophagoides pteronyssinus increasing those used in normal clinical conditions in comparison with regular doses of a non-modified vaccine. Materials and Methods: The study was double-blind, parallel and included two patient groups. Twenty-three patients were treated weekly during 9 visits for the build-up phase, followed by 2-weekly maintenance doses (a total of 11 injections per patient). Eleven patients (mean age 22 years) received immunotherapy with the standardized modified vaccine. The maximum dose used was the result of depigmenting and polymerizing 100 times the maximum dose used with the native extract. The maximum concentration used was 990 µg/ml of freeze-dried material. Twelve patients (mean age 24 years) received a standardized, unmodified allergenic extract. The maximum concentration used was 70 µg of freeze-dried material/ml, with a potency of 10 HEP_L/ml. The tolerance was evaluated recording all the side reactions related to immunotherapy and graded following the recommendations of the European Academy of Allergology and Clinical Immunology. Results: In both groups, all immediate local reactions were clinically not relevant. Patients treated with the native extract experienced 42 local immediate and 24 delayed reactions (1 of them had a diameter >10 cm), whereas patients treated with the modified extract experienced 30 local immediate and 21 delayed reactions (2 of them had a diameter >10 cm). Four systemic reactions in 2 patients, 1 immediate of grade 1 and 3 delayed of grade 2 were reported in the group treated with native extract and 1 delayed of grade 2 in the group treated with the modified preparation. Conclusions: The modified extract of D. pteronyssinus, used at concentrations which are 10 times higher than those regularly administered in clinical practice, demonstrated to be safe to treat D. pteronyssinus-sensitive patients. The major ity of the local reactions (immediate and delayed) were clinically not relevant (diameter <5 cm). No systemic reactions of grade 3 or 4 were noted.

Specific Immunotherapy and Central Immune System

“…In patients with respiratory allergy submitted to SCIT with depot extracts there were no evident differences connected to the extract composition, either mites or pollens. Regarding the allergoid extracts, a reduced inflammatory activity was observed at the administration site, similarly to what was previously reported in the literature and demonstrated in daily clinical practice (Casanovas et al, 2005(Casanovas et al, , 2007Ariano et al, 1999). The modification of the allergenic with glutaraldehyde reduced the local inflammatory activity to levels similar to the ones observed in the control patients submitted to SS.…”

“…The aqueous extracts are highly effective, but induce more side-effects (local and systemic) than depot and modified vaccines (Larché et al, 2006). These have been developed in an attempt to reduce or remove allergenicity, while preserving or increasing the immunogenicity (Casanovas et al, 2005). Aqueous subcutaneous SIT is now the gold standard treatment for hymenoptera venom allergy and depot aeroallergen extracts for respiratory allergy (Wheeler & Woroniecki, 2004).…”

Safety of an Ultra-Rush Immunotherapy Build-Up Schedule with Therapeutic Vaccines Containing Depigmented and Polymerized Allergen Extracts

“…These extracts have shown efficacy using objective parameters, such as specific bronchial provocation and skin tests, demonstrating improvement after 6 months of treatment [22] or after 4 months when a shorter build-up schedule (cluster) was used [23]. They also have a wider safety profile than unmodified preparations since doses greater than those recommended can be administered without moderate or serious adverse reactions [24]. …”

“…The introduction of a depigmentation step, before the polymerization process removes the adsorbed pigments, enhances the solubility of the allergoids and inactivates the enzymatic activity [18]. These recently developed allergoids have been used in clinical studies of efficacy, safety and tolerability [19,20,21,22,23,24,25,26]. These vaccines maintain or increase IgG recognition, while significantly reducing IgE reactivity, which allows shortening of the build-up phase and the administration of higher doses than those used with non-modified allergens.…”

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

“…Although the efficacy of this approach for the treatment of rhinoconjunctivitis and asthma has been confirmed in many controlled studies [2,3], conventional subcutaneous immunotherapy involves injection of allergen extracts with the potential to cause severe allergic reactions due to cross-linking of allergen-specific IgE. This small risk of anaphylaxis has limited the use of subcutaneous immunotherapy and led to the development of modified allergen extracts, termed allergoids, with reduced IgE-binding activity (allergenicity) [4], thus increasing safety [5]. On the other hand, although not many studies have analyzed T cell reactivity (immunogenicity), some studies have suggested that reactivity of T helper cells with allergoids is dependent on the type of antigen-presenting cells [6] and the individual [7].…”