Modified forms of allergen immunotherapy

Grammer, Leslie C.; Shaughnessy, Martha A.; Patterson, Roy

doi:10.1016/0091-6749(85)90661-x

Cited by 73 publications

(47 citation statements)

References 30 publications

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“…Several studies were carried out with allergens modified by means of aldehydes [78, 79, 80, 81, 82, 83]. Formaldehyde- and glutaraldehyde-treated allergens termed ‘allergoids’ displayed low IgE binding [78, 79]; they were much better tolerated than the native allergen extract and fewer injections were required to reach higher maintenance doses [78, 79, 80, 81, 82].…”

Section: Strategies For Bypassing Effector Cell Surface Ige Cross-linmentioning

confidence: 99%

Regulation of Specific Immune Responses by Chemical and Structural Modifications of Allergens

Akdiş¹,

Blaser²

2000

Int Arch Allergy Immunol

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Specific immunotherapy (SIT) is an efficient treatment of allergic diseases to defined allergens. Despite being used in clinical practice since early in this century, more rational and safer regimens are required, because SIT is faced with the risk of anaphylaxis and standardization problems of allergen-extract-based treatments. A better understanding of the pathogenesis of allergy and of the mechanisms of SIT has led to various approaches to overcome these problems. Knowledge of the influence of IgE-facilitated antigen presentation on allergen-specific Th2 responses increased the efforts to generate non-IgE-binding allergens. The current principal approach to allergen modification is to modify B cell epitopes in order to prevent IgE binding and effector cell cross-linking while preserving T cell epitopes to retain the capacity of inducing tolerance. In this way, the modified allergen will be directed to T cells by a phagocytosis/pinocytosis-mediated antigen uptake mechanism, bypassing IgE cross-linking and IgE-dependent antigen presentation. Accordingly, a differential regulation of allergen-specific T cell cytokine patterns and IgE:IgG production was demonstrated by modifications of the three-dimensional structure of allergens because of linearity in T cell epitopes and conformation dependence in B cell epitopes. In this context, chemically modified allergen extracts with low IgE-binding capacity have been developed to reduce anaphylactic side effects since the early 1980s. The progress of recombinant techniques for producing allergens and allergen derivatives has led to a dramatic improvement in the ability of developing novel vaccines for the treatment of allergy. This has enabled mutation or deletion of decisive amino acids in B cell epitopes and fractionation or oligomerization of allergens by genetic engineering as fruitful approaches to generate hypoallergenic vaccines. Moreover, non-IgE-binding short T cell epitope peptides and single-amino-acid-altered peptide ligands represent potential candidates for future SIT.

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Section: Strategies For Bypassing Effector Cell Surface Ige Cross-linmentioning

confidence: 99%

Regulation of Specific Immune Responses by Chemical and Structural Modifications of Allergens

Akdiş¹,

Blaser²

2000

Int Arch Allergy Immunol

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“…In an attempt to overcome these disadvantages, glutaraldehyde-modified allergen extracts were developed, proving to be safer than unmodified vaccines while retaining clinical efficacy [16, 17]. 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].…”

Section: Introductionmentioning

confidence: 99%

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

Casanovas¹,

Martin²,

Jiménez³

et al. 2006

Int Arch Allergy Immunol

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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.

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“…Different molecular weight fractions of glutaraldehyde-polymerized timothy extract have been compared. With 4 fractions of increased molecular weight a uniformly decreasing allergenicity and antigenicity was found (65), and in skin tests it was demonstrated that a fraction below 200 kD was 10'^-10^ times more potent than a fraction of 200-2000 kD (29,89).…”

Section: Low-allergenic Extractsmentioning

confidence: 99%