Abstract
IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available. We developed a mouse model for IgE sensitization to Bet v 1 based on subcutaneous injection of aluminum-hydroxide adsorbed recombinant Bet v 1 and performed a detailed characterization of the specificities of the IgE, IgG and CD4+ T cell responses in sensitized mice using seven synthetic peptides of 31-42 amino acids length which comprised the Bet v 1 sequence and the epitopes recognized by human CD4+ T cells. We then demonstrate that preventive systemic administration of a mix of synthetic non-allergenic Bet v 1 peptides to 3-4 week old mice significantly reduced allergic immune responses, including IgE, IgG, IgE-mediated basophil activation, CD4+ T cell and IL-4 responses to the complete Bet v 1 allergen but not to the unrelated major grass pollen allergen Phl p 5, without inducing Bet v 1-specific allergic sensitization or adaptive immunity. Our results thus demonstrate that early preventive administration of non-allergenic synthetic T cell epitope-containing allergen peptides could be a safe strategy for the prevention of allergen-specific IgE sensitization.
Highlights
Immunoglobulin E (IgE)–associated allergy is the most frequent immunologically mediated hypersensitivity disease and affects more than 30% of the worlds population [1]
In order to establish a model for Bet v 1-specific sensitization, a single injection was selected to determine the effect of one dose on allergen-specific IgE and IgG production
It is necessary to demonstrate that early life administration of the peptides does not induce allergic sensitization and it is important to use a mix of peptides comprising the T cell epitope binding (MHC) and recognition (TCR) repertoire of humans
Summary
Immunoglobulin E (IgE)–associated allergy is the most frequent immunologically mediated hypersensitivity disease and affects more than 30% of the worlds population [1]. Allergic patients suffer from a variety of clinical symptoms which include hay fever (i.e., rhinitis, conjunctivitis), asthma, skin inflammation, gastrointestinal allergy and life-threatening systemic anaphylactic shock [2]. The detailed analysis of the evolution of allergic sensitization from early childhood to adolescence suggests that allergic sensitizations occur early in life and, depending on genetic and environmental factors, in particular in response to repeated allergen contact, progresses from clinically silent forms of IgE sensitization towards symptomatic allergy [3]. Symptomatic allergy often starts with mild symptoms such as allergic rhinitis and progress to severe forms such as allergic asthma [4]. Similar as for the aforementioned noncommunicable diseases which heavily affect mankind and create a huge burden to the health care systems, early preventive intervention strategies are needed for allergy [5]. Preventive strategies for allergy include besides attempts of general immunomodulation allergen-specific and non-specific forms of prevention, for example early allergen-specific immunotherapy, AIT, allergen avoidance, allergen-specific tolerance induction and application of immunomodulating substances such as pre- and probiotics [6,7,8,9,10,11,12,13,14,15]
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