Will Allergen Fusion Bring New Energy to Immunotherapy?

from either grass or tree pollens, insect venoms, cat dander as well as house dust mites [2–13] ( fig. 1 ). Such fusion proteins can then be expressed in Escherichia coli , yeasts (e.g. Saccharomyces cerevisiae or Pichia pastoris ) and plant or mammalian host cell systems prior to purification and refolding. One advantage, obviously, is to produce the multiallergen drug substance as a single molecule, thus facilitating manufacturing and development. Another foreseen interest is to reduce IgE binding to the allergen(s), while enhancing its (their) capacity to elicit IgG and T cell responses [3, 10, 13] . In a recent issue of International Archives of Allergy and Immunology , Fujimura et al. [14] describe a fusion protein, involving Cry j 1 and Cry j 2 major allergens from Japanese cedar (JC) pollen, as a candidate product for specific immunotherapy. After only minor modifications, these 2 allergens were further conjugated with polyethylene glycol (PEG), commonly used in combination with therapeutic proteins to increase their stability in the bloodstream. JC pollen allergy is the most prevalent seasonal allergic rhinitis in Japan, and, as such, represents a major health problem with up to 25% of the population being sensitized. The PEG-fusion was expressed in E. coli , purified, and injected subcutaneously 4 times into Cry j 1-sensitized mice prior to a subcutaneous challenge with Although specific immunotherapy is currently only performed with aqueous allergen extracts, second-generation allergy vaccines may rather rely upon well-defined recombinant allergens [1] . The latter represent an attractive alternative to natural allergen extracts, since they can be produced in large quantities with consistent quality. In most circumstances, however, multiple allergens are involved in sensitization, making the recombinant allergen approach very complex as it requires a comprehensive characterization of each individual component of the vaccine. In this context, an interesting strategy is to fuse together several wild-type or mutated allergens, or peptidic fragments, using recombinant DNA technologies ( fig. 1 ). In such fusions, allergens can be further linked to heterologous molecules, used as carriers to enhance stability and immunogenicity (e.g. by facilitating uptake by antigen-presenting cells), thereby creating hybrid or chimeric molecules. Such carrier molecules include, for example, viral proteins such as the rhinovirus or Qβ phage capsid proteins, the pre-S protein from the hepatitis B virus, a modular antigen-translocating moiety, the Fc fragment of an immunoglobulin and the bacterial surface S-layer protein ( fig. 1 ). The fusion or hybrid approach has previously been applied by various groups to assemble head-to-tail allergens Published online: December 11, 2015