Immunotherapy with peptides

Abstract

Specific allergen immunotherapy is clinically effective and has benefit that extends beyond the treatment period (1). Unlike conventional pharmacotherapy, specific allergen immunotherapy is disease modifying and has been shown to prevent the development of asthma (2) and to reduce sensitizations to other allergens (3). Optimal treatment times vary based on allergen and therapeutic preparation, but in general terms, a course of 3 years therapy is regarded as optimal. Although there are no formal published data on the relationship between treatment time and duration of clinical response, it is widely held that clinical benefit will last for twice as long as the treatment period. Thus, treatment for 1 year results in additional benefit for the subsequent year, whereas treatment for 3 years will provide clinical benefit for a further 3 years. The lengthy duration of treatment, the frequent administration of allergen and the associated high frequency of allergic adverse events, which may be systemic and in some cases lifethreatening, have limited uptake of this form of therapy. These shortcomings are the result of the allergenicity of the preparations employed for therapy. These contain whole allergen molecules with intact B-cell epitopes that are readily able to crosslink specific IgE molecules on the surface of effector cells (Fig. 1). A number of strategies aimed at reducing the allergenicity of treatment preparations, whilst maintaining immunogenicity, have been described. Physical modification of allergen molecules may reduce or eliminate IgE reactivity and thus allergenicity (4). Such approaches have taken many forms including chemical modification, conjugation with synthetic bacterial DNA motifs, point mutations in native allergen gene sequences and the use of allergen multimers, fragments and peptides of various lengths. The use of soluble, short synthetic peptides for the treatment of allergic disease allows the delivery of T-cell epitopes of the allergen in an adjuvant-free, tolerogenic form, whilst avoiding IgE-mediated allergic reactions (5, 6). Synthetic peptides have been developed and evaluated in both experimental animal models and human clinical studies. Synthetic peptides are defined active pharmaceutical ingredients (API) and can be produced in a reproducible and standardized fashion that cannot be achieved with allergen extracts. Further advantages include low production costs, ease of purification and good stability in lyophilized form without the need for cold storage. Presentation of T-cell epitopes to T cells by nonprofessional antigen-presenting cells (APC) results in the induction of 'anergy', a term describing antigen-specific nonresponsive- AbstractSpecific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to ...

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

“…Encouraging findings have also been reported in allergic patients (16)(17)(18)(19)(20). However, reduced disease severity is not universal, and limitations in our understanding of the workings of PIT are impeding clinical translation.…”

Allergen Immunotherapy in Allergic Respiratory Diseases

“…98 Peptide immunotherapy using short linear T-cell epitopes of the antigen are also of interest, with the hope that such modalities would retain the antigen's immunogenicity while curtailing its allergenicity. 99 Assessment of these approaches awaits ongoing trials. Allergic diseases have an immune basis to their origin and ongoing symptoms.…”

Specific Immunotherapy in Children: The Evidence

“…Alternative strategies to improve the immunological responses and clinical outcomes in SIT treated allergic patients are the activation of the innate immune system through Tolllike receptor (TLR) agonists, innate immune receptors designed to respond to a variety of pathogens and induce THI and regulatory T-cell responses. Another therapeutic option involves packaging CpG ISSs (inhaled CpG immunostimulatory sequences) into virus-like particles (VLPs), allergoids, recombinant allergens, peptides, hybrid molecules, IgE-reactive haptens and mimotopes (81,82,83,84,85). …”