Polymerized Allergen Extracts Research Articles

Efficacy and safety of subcutaneous immunotherapy with a mixture of glutaraldehyde-modified extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis

BackgroundAllergen Immunotherapy (AIT) is an effective treatment of allergic respiratory diseases induced by the inhalation of house dust mite allergens. ObjectivesTo evaluate the efficacy and safety of glutaraldehyde polymerized allergen extracts using a mixture of Dermatophagoides pteronyssinus, D. farinae and Blomia tropicalis in mite allergic individuals residing in Colombia. MethodsTwo hundred and fifty (250) patients with allergic rhinoconjunctivitis with, or without asthma and sensitized to D. pteronyssinus, D. farinae and B. tropicalis were included. A glutaraldehyde-modified extract containing a mixture of D. pteronyssinus, D. farinae and B. tropicalis was employed, using a cluster up-dosing schedule followed by a monthly maintenance dose. The primary endpoints to evaluate the clinical impact were the Combined Symptom and Medication Scores (CSMS) for allergic rhinitis, the Asthma Control Test (ACT) and the reduction in medication consumption. ResultsSignificant improvement was found after 3 months of treatment regarding CSMS (p < 0.0001) and ACT (p < 0.0001). Additionally, a significant decrease in medication consumption was found after 3 months of treatment (p < 0.0001). Adverse reactions, either local or systemic were mild and no severe reactions related to the vaccines were observed. ConclusionAfter 12 months of allergen immunotherapy, glutaraldehyde-modified mixture of D. pteronyssinus, D. farinae and B. tropicalis proved to be safe and effective in the treatment of patients with rhinoconjunctivitis with or without asthma due to allergy to mites.

Specific immunotherapy in local allergic rhinitis: A randomized, double-blind placebo-controlled trial with Phleum pratense subcutaneous allergen immunotherapy.

Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR. In a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptom medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication-free days, rhinitis severity and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific IgG4 and specific IgE and safety were also evaluated. Subcutaneous immunotherapy (SCIT) had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months of treatment. At the end of the study, 83% of patients treated with ≥6months of SCIT tolerated a concentration of P. pratense over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication. Subcutaneous immunotherapy with depigmented polymerized allergen extracts is a safe and clinically effective treatment for LAR to P.pratense.

In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy

BackgroundAllergy to cat epithelia is highly prevalent, being the major recommendation for allergy sufferers its avoidance. However, this is not always feasible. Allergen specific immunotherapy is therefore recommended for these patients. The use of polymerized allergen extracts, allergoids, would allow to achieve the high allergen doses suggested to be effective while maintaining safety.ResultsCat native extract and its depigmented allergoid were manufactured and biochemically and immunochemically characterized. Protein and chromatographic profiles showed significant modification of the depigmented allergoid with respect to its corresponding native extract. However, the presence of different allergens (Fel d 1, Fel d 2, Fel d 3, Fel d 4 and Fel d 7) was confirmed in the allergoid. Differences in IgE-binding capacity were observed as loss of biological potency and lower stability of the IgE-allergen complex on surface plasmon resonance. The allergoid induced production of IgG antibodies able to block IgE-binding to native extract. Finally, studies carried out with peripheral-blood mononuclear cells from cat allergic patients showed that the allergoid induced IFN-γ and IL-10 production similar to that induced by native extract.ConclusionsCat depigmented allergoid induced production of cytokines involved in a Th1 and Treg response, was able to induce production of IgG-antibodies that blocks IgE-binding to cat native extract, and showed reduced interaction with IgE, suggesting greater safety than native extract while maintaining in vitro efficacy.

1 Ultra-Rush Specific Immune Therapy with Depigmented and Polymerized Allergen Extracts is Effective and Safe in Patients With Severe SAR Highly Sensitized against Pollen Allergens

BackgroundProcedures for specific immune therapy (SIT) vary widely. We were interested whether a pre-seasonal ultra-rush treatment with depigmented and polymerized allergen extracts is effective and safe in patients with severe SAR.Methods31 pts (21 f, 10 m, mean age 39.7 years, range: 17–69 years) with severe SAR and partial asthma attacks (31.3%) during pollen season (mean total IgE level 152 kU/L, range: 5–5113 kU/L; mean Phadia CAP class 3.7 and 3.5 against birch pollen and Bet v1, resp.; mean Phadia CAP class 3.7 and 3.3 against grass pollen and Phl p1,5, resp.) were treated with an ultra-rush schedule receiving the maximum dose of 0.2 plus 0.3 mL of a allergen extract (DepiQuick, Novartis, Germany) on day one, followed by further injecting the maximum dose of 0.5 mL at weekly intervals for 5 weeks. Patients were interviewed by a questionnaire 2 months after the pollen season.Results75.8% of patients reported a good or very good effect of SIT with respect to their symptoms during the pollen season after having received only one cycle of ultra-rush SIT; 18.4 did not notice any effect after the first cycle; one patient reported an increase of symptoms. 56.5% of patients did use less anti-allergic medication in comparison with their mean need before SIT; in 18.8% the need of medication was comparable to the year before. In 77.8% of all cases ultra-rush SIT was well tolerated subjectively. Local swelling at the injection site was reported in 25.9% (immediate) and 42.4% (delayed); 4 patients felt a mild discomfort after injection with pruritus, fatigue, or dizziness, respectively. The systemic symptoms disappeared spontaneously without medication.ConclusionsEven for patients with clinically severe SAR and high specific sensitization against birch or grass pollen the pre-seasonal ultra-rush SIT regimen with depigmented, polymerized allergen extracts showed a good efficacy and tolerability.

10 Seasonal Versus Symptom-based Evaluation of a Depigmented Grass-Birch Allergoid

BackgroundThe safety and efficacy of specific immunotherapy (SIT) with depigmented and polymerized allergen extracts of pollen is well documented in several clinical trials. The results of such clinical studies are highly dependent on the quantity and quality of pollen exposure and their measurements. To identify a pollen-independent efficacy assessment we compared the combined symptom and medication score (SMS) measured during the pollen season with the SMS defined by a minimum symptom score of the placebo group in a subcutaneous immunotherapy with a depigmented Grass-Birch allergoid over 2 years.Methods269 (ITT) patients with confirmed rhinitis and/or rhinoconjunctivitis were treated during 2009 and 2010 in Germany, Romania, Poland, Lithuania, and Bulgaria. Patients were randomised to the treatment groups on a 2:1 basis (175 verum: 94 placebo). The main parameter in this study was the combined symptom and medication score during the birch and grass pollen season 20101. In addition the SMS of the actively treated patients was analyzed following the placebo treated patients eliciting a considerable symptom burden >2.ResultsThe clinical results following the seasonal approach are given in the other abstract of our group1. Taking all days with mean symptom score >2 in the placebo group as calculation basis, the combined SMS values were considerably lower for actively treated patients than for placebo treated patients. For both seasons, the differences between the treatment groups were highly statistically significant (median; 2009: 5.06 vs 7.97, 2010: 4.26 vs 6.43; ITT set) with P-values of 0.0038 and 0.003.ConclusionsThe results show that the efficacy assessment of specific immunotherapy might be better discriminated in relation to the actual symptoms of the placebo group rather than following the days of pollen exposure.

7 Comparison of Efficacy and Safety of a Dipigmented Polymerized Allergen Extract of Grass and Birch with Placebo in Patients With Type-1 Allergic Rhinoconjunctivitis

BackgroundThe safety and efficacy of specific immunotherapy (SIT) with depigmented and polymerized allergen extracts of pollen is well documented in several clinical trials. We investigated efficacy and safety of an extract containing 2 taxonomically non-related pollen species (birch and grasses) in a subcutaneous immunotherapy over 2 pollen seasons in co-sensitized allergic patients with rhinitis and/or rhinoconjunctivitis with or without allergic asthma.Methods269 (ITT) patients with confirmed rhinitis and/or rhinoconjunctivitis were treated during 2009 and 2010 in Germany, Romania, Poland, Lithuania, and Bulgaria. For each patient a 1-day build-up phase applying 0.2 mL and 0.3 mL of 1000 DPP/mL allergen extract was applied. During the remaining 18-month period maintenance 500 DPP were administered in 4 to 6 weeks intervals. Patients were randomised to the treatment groups on a 2:1 basis (175 verum: 94 placebo). The main parameter in this study was the combined symptom and medication score during the birch and grass pollen season 2010 over 7 weeks. Secondary parameters were symptom score, medication score, IgE, IgG4 as well as quality of life.ResultsDuring the 2010 season a statistically significant difference (P = 0.0385) was observed between treatment groups: in patients treated with the allergen extract the median time weighted AUC of the combined symptom and medication score was 5.70, in patients treated with placebo 7.07. This effect was predominantly due to the reduction of symptom score by 21% over placebo. The intake of recue medication was very low during both seasons leading only to a 10% reduction (ns). Birch and phleum specific IgE did not change during the course of the study in both groups whereas respective IgG4 levels increased only in the verum group and remained nearly unchanged in the placebo group (P < 0.0001). Total QoL score was improved in verum patients (P = 0.0254). 5.4% of the patients in the verum group and 4.0% of the patients in the placebo group developed mild systemic reactions.ConclusionsThe results show that specific immunotherapy with a depigmented polymerized extract of 2 taxonomically non-related pollen (birch and grass) was effective and safe demonstrated by clinical and immunological parameter.

Safety of a Depigmented, Polymerized Vaccine for the Treatment of Allergic Rhinoconjunctivitis and Allergic Asthma

Clinical efficacy of specific immunotherapy (SIT) with depigmented, polymerized allergen extracts is well documented in placebo-controlled trials, and safety data are encouraging although further data are required. We enrolled 768 patients (51% men; mean age, 31 years) in this prospective multicenter study on safety and clinical effects of Depigoid (Laboratorios LETI, S.L., Madrid, Spain). Immunotherapy consisted of four injections of increasing doses of Depigoid at weekly intervals followed by monthly maintenance injections. All adverse events were documented. Moreover, nose, eye, and lung symptoms were assessed at baseline after 3 and 6 months. Results were compared with the scores of the preceding season. Rates for local and systemic reactions that might possibly be related to the study medication were 2.36 and 4.56/1000 injections, respectively. With 5923 injections given, 14 local reactions were reported (5 patients), and 27 systemic reactions were reported, including 20 of grade 1 (6 patients) and 7 of grade 2 (4 patients). The best safety profile was seen for patients vaccinated against house-dust mites. Reductions in nose, eye, and lung symptoms as well as in concomitant medication compared with either the preceding season (pollen-sensitized patients) or the baseline (house-dust mite-sensitized patients) were observed at the end of study. In this large multicenter study on 768 patients with allergic rhinoconjunctivitis and allergic asthma under daily practice conditions SIT with Depigoid was well tolerated with low rates of local and systemic reactions. Furthermore, SIT resulted in considerable reductions in symptoms and concomitant medication.

Safety of a rush immunotherapy build-up schedule with depigmented polymerized allergen extracts

Conventional subcutaneous immunotherapy (SCIT) for allergy treatment needs several injections over several weeks to reach the maintenance dose. Shorter up-dosing regimens are desired but limited by the potential of side effects. This study was designed to compare the safety of Depigoid (Laboratorios LETI, Spain)-SCIT 1 day versus 3 weeks up-dosing in patients with Type 1 allergy caused by clinically relevant sensitization against tree pollen, grass pollen, and house-dust mites. A total of 303 patients with confirmed allergic rhinitis/conjunctivitis were included. A rush build-up schedule administering 0.2 mL and then 0.3 mL of the concentrate at day 1 followed by 0.5 mL at day 28 was compared with a conventional 4-week build-up schedule. The number of patients reaching the maintenance phase without systemic reactions or major deviation from treatment schedule were compared. Of the rush 91.8% and in the conventional group 90.9% reached the maintenance phase without dose modification. Neither the proportions of patients with systemic reactions (5.8% rush versus 2% conventional) nor the proportions of patients with local reactions differed significantly between the two regimens (24% rush versus 11% conventional). There was no difference with respect to the applied allergen group. The proposed rush build-up schedule for the immunotherapy treatment with depigmented allergoids without premedication is safe and not inferior to the conventional schedule.

Specific Immunotherapy with depigmented polymerized allergen extracts of domestic mites in patients with persistent rhinoconjunctivitis

Specific Immunotherapy with depigmented polymerized allergen extracts of domestic mites in patients with persistent rhinoconjunctivitis

Evolution of quality of life in patients treated with therapeutic vaccine containing depigmented and polymerized allergen extracts of dermatophagoides pteronyssinus and D. farinae in allergic asthmatic patients

Evolution of quality of life in patients treated with therapeutic vaccine containing depigmented and polymerized allergen extracts of dermatophagoides pteronyssinus and D. farinae in allergic asthmatic patients

Safety of immunotherapy with therapeutic vaccines containing depigmented and polymerized allergen extracts

The major complication of allergen immunotherapy is a severe reaction. To evaluate the safety of depigmented and glutaraldehyde-modified allergen extracts in a large group of patients undergoing immunotherapy treatment. Seven hundred sixty-six patients, having rhinoconjunctivitis and/or asthma, were entered in a prospective, multi-centre, observational cohort study, to evaluate the safety of immunotherapy with modified allergen vaccines. Patients were sensitized to mites and/or pollen and received a therapeutic vaccine containing depigmented and polymerized allergen extracts of mites and/or pollens adsorbed onto aluminium hydroxide. The schedule of administration consisted of a build-up phase of 4- to 6-weekly injections, followed by 12-monthly injections of the maintenance dose. Tolerance was assessed by recording all side reactions related to immunotherapy. All patients completed the study. Fifty-four clinically relevant local reactions (43 immediate and 11 delayed) were observed (0.4% of injections). The systemic reactions were 34 in 12 patients. Six reactions were immediate (all of grade 2) and 28 delayed (18 of grade 1 in two patients, nine of grade 2 and one of grade 3). The systemic reactions of grade 2 or 3 occurred in 0.12% of the injections. All systemic reactions were mild and resolved spontaneously without the need for medication. Specific immunotherapy using modified allergen vaccines is safe to treat allergic patients. The percentage of adverse reactions detected is lower than those reported in the literature with native-unmodified allergen extracts.

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

Background: Four administration schedules of immunotherapy have been reported: conventional, cluster, rush and ultra-rush. Objectives: To evaluate the safety and the clinical advantage of using standardized modified allergen extracts in an ultra-rush protocol without premedication and/or hospitalization. Material and Methods: One thousand and sixty-eight patients with rhinoconjunctivitis and/or asthma sensitized to mites and/or pollen were included in a prospective observational study. Patients received a therapeutic vaccine containing depigmented and glutaraldehyde-modified extracts (mites and/or pollens) adsorbed onto alum prescribed by a specialist. The schedule of administration consisted of injecting 0.2 and 0.3 ml of the vial of maximum concentration during the first day of immunotherapy, separated by a time interval of 30 min. All patients reached the maximum dose (0.5 ml) after 2 injections. Tolerance was assessed by recording all side reactions related to immunotherapy, classified according to the criteria of the EAACI. Results: The total number of injections was 2,136. All patients reached the maximum established dose on the 1st day. No premedication was used. Seven clinically relevant local reactions were recorded. The systemic reactions were 5 grade-1 (2 immediate and 3 delayed) and 3 delayed grade-2 reactions. Conclusions: The therapeutic vaccines containing chemically modified extracts can be administered using an alternative ultra-rush schedule in an immunotherapy unit, reaching the maximum dose on the 1st day with 2 injections, without the need of premedication and/or hospitalization.

Comparison of parallel line skin test assay (PLST) and ELISA inhibition (EI) methods for determination of relative potency of polymerized grass and ragweed antigenic extracts

Relative potency estimates were performed by parallel line skin test assay (PLST) and ELISA inhibition methods for three polymerized allergen extracts (Bermuda grass, orchard grass, and a copolymer of short and giant ragweed) versus four unmodified RAST standardized reference extracts (Bermuda grass, orchard grass, and giant and short ragweed) in nine subjects. One subject experienced a systemic reaction, requiring treatment at the end of the PLST assay. Another subject had a systemic reaction during limited skin testing performed approximately 72 hours after completion of PLST. Relative potency values for the polymerized extracts obtained by PLST were much lower than those obtained by ELISA inhibition, but results were significantly (r = 0.95; p < 0.01) correlated. Because polymerized allergen extracts are designed to be hypoaller genie, a skin test assay may underestimate their potency relative to an unmodified reference extract.

Standardization of modified allergens using polymerized ragweed as a model system

Polymerized allergens are manufactured by crosslinking allergen molecules with glutaraldehyde and then selecting a desired molecular weight range by gel filtration chromatography. Polymerized allergen extracts have retained antigenicity but reduced allergenicity when compared with conventional allergenic extracts. Thus, the important parameters to standardize in polymerized extracts are allergenicity, antigenicity, and molecular weight range. As our initial studies have demonstrated that allergenicity correlates with antigenicity and molecular weight, only the latter are necessary to measure. In short, polymerized allergen extracts could be standardized simply in terms of in vitro reactivity and chromatographic profile.