Allergen-specific immunotherapy with recombinant grass pollen allergens

doi:10.1016/j.jaci.2005.06.004

Journal of Allergy and Clinical Immunology

Volume 116, Issue 3, September 2005, Pages 608-613

https://doi.org/10.1016/j.jaci.2005.06.004 Get rights and content

Background

Allergen-specific immunotherapy uses aqueous extracts of natural source materials as a basis for preparations to downregulate the allergic response. Recombinant DNA technology has enabled the cloning of many allergens, thus facilitating investigations aimed at improving efficacy and safety of immunotherapy.

Objective

To determine the effectiveness of a mixture of 5 recombinant grass pollen allergens in reducing symptoms and need for symptomatic medication in patients allergic to grass pollen.

Methods

A randomized, double-blind, placebo-controlled study of subcutaneous injection immunotherapy was performed in subjects with allergic rhinoconjunctivitis, with or without asthma. Primary endpoint was a symptom medication score compiled from separate symptom and medication scores. Secondary endpoints included a rhinitis quality of life questionnaire, conjunctival provocation, and specific antibody responses.

Results

The symptom medication score showed significant improvements in subjects receiving recombinant allergens as opposed to placebo, with reductions in both symptoms and medication usage. The rhinitis quality of life questionnaire revealed clinically relevant significant improvements in overall assessment and in 5 of 7 separate domains, and conjunctival provocation showed a clear trend in favor of active treatment. All treated subjects developed strong allergen-specific IgG₁ and IgG₄ antibody responses. Some patients were not sensitized to Phl p 5 but nevertheless developed strong IgG antibody responses to that allergen.

Conclusion

A recombinant allergen vaccine can be a effective and safe treatment to ameliorate symptoms of allergic rhinitis. The clinical benefit is associated with modification of the specific immune response with promotion of IgG₄ and reduction of IgE antibodies consistent with the induction of IL-10–producing regulatory T cells.

Section snippets

Study design

A randomized, double-blind, placebo-controlled study was performed in Wroclaw Medical University, Poland, with approval of the local ethics committee and the Medical Council for Schleswig-Holstein, Bad Segeberg, Germany. Subjects provided informed written consent, and the study was conducted in accordance with Guidelines for Good Clinical Practice.¹¹ The study physician allocated treatment sets previously randomized and labeled by the manufacturer using computer generated random number tables.

Results

A total of 64 subjects was enrolled, and 62 were assigned randomized treatment sets and included in the safety evaluation. Five subjects were subsequently excluded from the main data set because more than 25% of diary entries were missing, making assessment of the primary endpoint impossible, thus leaving 29 active treatment and 28 placebo subjects in the full analysis set. Groups were well matched for age (25 years; 21-30, interquartile range; vs 24.5 years; 22-26.5) and sex (8 F/21 M vs 12

Discussion

This first clinical study of immunotherapy using a cocktail of 5 recombinant grass pollen allergens for the treatment of hay fever has demonstrated the clinical efficacy and good tolerance of the preparation, together with the induction of strong allergen-specific IgG antibody responses.

Allergic patients have both the clinical manifestations of their disease and the burden of having to take antiallergic medication.¹⁶ The combined symptom medication score took account of both considerations and

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Long-term AIT, however, will result in a decline in serum allergen-specific IgE levels, which promotes long-term clinical tolerance (Scadding et al., 2017). In addition, overwhelming evidence from numerous studies show increases of 10- to 100-fold in serum IgG (total) and allergen specific IgG4 (spIgG4) upon successful AIT, and these are often referred to as the neutralizing or blocking antibodies capable of dampening IgE mediated responses (Jutel et al., 2005; Wachholz, Soni, Till, & Durham, 2003). It was shown that in nasal fluids, spIgG4 is capable of trapping allergens before they can crosslink surface bound IgE on mast cells and basophils, thereby inhibiting release of inflammatory mediators (Shamji et al., 2019).
Allergic respiratory diseases, such as allergic dermatitis, food allergy, allergic rhino conjunctivitis and allergic asthma, are chronic inflammatory diseases with increasing prevalence. Symptoms include such as watery or itchy itching of the mouth, skin, or the eyes, swelling of the face or throat, sneezing, congestion or vomiting, wheezing, shortness of breath and coughing. For allergic asthma, additional symptoms include tightness of chest, cough, wheezing, and reversible airflow limitation. These symptoms can be triggered by inhalation of allergens such as food allergens or airborne allergens such as those from tree- or grass pollen and house dust mites. Pharmacological intervention in allergic disease includes the use of antihistamines, immune suppressive drugs and in case of asthma, the use of (long acting) beta-agonists for relaxation of the constricted airways. These treatment options merely suppress symptoms and do not cure the disease. Allergen immunotherapy (AIT), in contrast, has the capacity of inducing long-term tolerance, with symptom relief persisting decennia after discontinuation of treatment, despite recurrent re-exposure to the allergen. However, AIT is not effective for all allergic disorders, and treatment for several years is required to obtain long-term protection. Moreover, some forms of AIT have safety concerns, with risk of mild to severe allergic reactions. To improve safety and efficacy of AIT, the underlying mechanisms have been studied extensively in the clinic as well as in experimental models of allergic airway inflammation.
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: Disclosure of potential conflict of interest: M. Jutel and L. Jaeger are on the Advisory Board for and receive lecture fees from Allergopharma Joachim Ganzer KG. R. Suck, H. Fiebig, and O. Cromwell have submitted a patent application concerning the Ph1 p 1 allergen (WO 2004/022588 A1) and are employees of Allergopharma Joachim Ganzer KG. H. Meyer is an employee of Allergopharma Joachim Ganzer KG.

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Rhinitis, sinusitis, and ocular diseasesAllergen-specific immunotherapy with recombinant grass pollen allergens

Background

Objective

Methods

Results

Conclusion

Section snippets

Study design

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

Methods

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

WHO position paper: allergen immunotherapy: therapeutic vaccines for allergic diseases: Geneva, January 27-29, 1997

Allergy

Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs

BMJ

Efficacy and safety of preseasonal immunotherapy with an aluminium-adsorbed six-grass pollen allergoid

Allergy

Long-term efficacy of preseasonal grass-pollen immunotherapy in children

Allergy

Long-term clinical efficacy of grass-pollen immunotherapy

N Engl J Med

Characteristics and immunobiology of grass pollen allergens

Int Arch Allergy Immunol

What are the most important allergens in grass pollen that are linked to human allergic disease?

Clin Exp Allergy

The future of antigen-specific immunotherapy of allergy

Nat Rev Immunol

Rhinitis, sinusitis, and ocular diseases
Allergen-specific immunotherapy with recombinant grass pollen allergens