Allergen-Specific Immunotherapy with Plant-Based Oral Vaccines

Abstract

allergen-specif ic immunotherapy has been practiced for almost a century. Success can be achieved by repeated subcutaneous injections of increasing doses of native allergen extracts over a period of at least 3–5 years. This treatment is sometimes accompanied by severe side effects, such as anaphylaxis, which is caused by capture of allergen together with specific anti-allergen IgE on the surface of mast cells and basophils. The development of safer, more effective and convenient allergen-specific immunotherapy has therefore long been desired. To achieve this, first, natural allergen extracts used for induction of immune tolerance (desensitization) need to be replaced by recombinant allergens with reduced allergenicity [5]. In order to develop such ideally hypoallergenic tolerogens, deletion, site-directed mutagenesis or molecular shuffling have all been introduced to alter the tertiary structure of the allergen and, thus, alter specific IgE binding [6]. Peptide immunotherapy using dominant T-cell epitopes derived from allergens represents another approach to developing safer treatment, because regions involved in allergenicity (i.e., responsible for reactivity with IgE) can be completely removed while retaining immunogenicity [7]. Second, the route of administration should preferably be changed from subcutaneous injection to mucosal application (oral, sublingual and nasal delivery). This would result in a safer and more convenient vaccine. Some modified recombinant allergens (Mal d 1, trimeric Bet v 1 and Bet v 1 fragment) have already been tested in animal models and evaluated as vaccines for subcutaneous and sublingual immunotherapy in allergic patients [7]. For practical use of plant-based allergy vaccines, high and consistent immunogen expression is critical for efficacy. To maximize the yield in a crop, the transferred genes encoding these tolerogens will need to be synthesized using codons optimized for expression in the selected Vaccines currently on the market are produced in Escherichia coli, yeast or insect cells. However, there is some evidence that plants could provide a more efficient production platform for vaccines than these. Plant-based vaccines are also advantageous in terms of their scalability, no cold chain required, stability, safety, cost–effectiveness and needle-free administration [1]. In particular, when antigen is expressed in seed, immunogenicity is not lost even if stocked at ambient temperature for several years [2]. Over the past two decades, many plant-made vaccines against infectious diseases have been produced [1,3]. Trials undertaken to feed these transgenic plants to animals and humans in clinical trials revealed their efficacy in protecting against infections through induction of target-specific systemic and mucosal immune responses. Furthermore, the feasibility of allergen-specific immunotherapy using plant-based vaccines has also been demonstrated recently.