Allergen hybrids – next generation vaccines for Fagales pollen immunotherapy. Issue 3 (March 2014)

• Record Type: Journal Article
• Authors: Pichler, U.; Hauser, M.; Hofer, H.; Himly, M.; Hoflehner, E.; Steiner, M.; Mutschlechner, S.; Hufnagl, K.; Ebner, C.; Mari, A.; Briza, P.; Bohle, B.; Wiedermann, U.; Ferreira, F.; Wallner, M.
• Is Part Of: Clinical & experimental allergy. Volume 44:Issue 3(2014:Mar.)
• Page Start: 438
• Page End: 449
• Publication Date: 2014-03
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12250
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12250-abs-0001"> <title>Summary</title> <sec id="cea12250-sec-0001" sec-type="section"> <title>Background</title> <p>Trees belonging to the order of Fagales show a distinct geographical distribution. While alder and birch are endemic in the temperate zones of the Northern Hemisphere, hazel, hornbeam and oak prefer a warmer climate. However, specific immunotherapy of Fagales pollen‐allergic patients is mainly performed using birch pollen extracts, thus limiting the success of this intervention in birch‐free areas.</p> </sec> <sec id="cea12250-sec-0002" sec-type="section"> <title>Objectives</title> <p>T cells are considered key players in the modification of an allergic immune response during specific immunotherapy (SIT), therefore we thought to combine linear T cell epitope‐containing stretches of the five most important Fagales allergens from birch, hazel, alder, oak and hornbeam resulting in a Fagales pollen hybrid (FPH) molecule applicable for SIT.</p> </sec> <sec id="cea12250-sec-0003" sec-type="section"> <title>Methods</title> <p>A Fagales pollen hybrid was generated by PCR‐based recombination of low IgE‐binding allergen epitopes. Moreover, a structural‐variant FPH4 was calculated by <italic>in silico</italic> mutagenesis, rendering the protein unable to adopt the Bet v 1‐like fold. Both molecules were produced in <italic>Escherichia coli</italic>, characterized physico‐chemically as well as immunologically, and tested in mouse models of allergic sensitization as well as allergy prophylaxis.</p> </sec> <sec id="cea12250-sec-0004" sec-type="section"> <title>Results</title> <p>Using spectroscopic analyses, both proteins were monomeric, and the secondary structure elements of FPH resemble the ones typical for Bet v 1‐like proteins, whereas FPH4 showed increased amounts of unordered structure. Both molecules displayed reduced binding capacities of Bet v 1‐specific IgE antibodies. However, in a mouse model, the proteins were able to induce high IgG titres cross‐reactive with all parental allergens. Moreover, prophylactic treatment with the hybrid proteins prevented pollen extract‐induced allergic lung inflammation <italic>in vivo</italic>.</p> </sec> <sec id="cea12250-sec-0005" sec-type="section"> <title>Conclusion</title> <p>The hybrid molecules showed a more efficient uptake and processing by dendritic cells resulting in a modified T cell response. The proteins had a lower IgE‐binding capacity compared with the parental allergens, thus the high safety profile and increased efficacy emphasize clinical application for the treatment of Fagales multi‐sensitization.</p> </sec> </abstract>