Venom Immunotherapy: From Proteins to Product to Patient Protection

Abstract

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil^® Bee and Wasp. Venomil^® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister-Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

Keywords: Hymenoptera; VIT; adjuvant; allergy; honeybee venom; sensitization; venom; wasp venom.

Figure 1

Manufacturing steps for Venomil^® with reference to in-process controls. * The target for reconstitution is to fulfil the full drug product specifications (e.g., total allergenicity, enzyme activity and protein content) following the product processing. ** Protein profiling (SDS-PAGE) and allergen profiling (SDS-PAGE and Western blotting) are performed against a controlled, representative in-house reference preparation. Further characterization is performed by proteomics analysis.

Figure 2

Stability of Api m 10 in Venomil^® Bee during long-term storage in solution at 4 °C. Venomil^® Bee was solubilized in the product-specific HSA-containing diluent and stored at 4 °C. Aliquots were taken at the indicated time points and stored at −20 °C until final analysis. The samples were analyzed for their Api m 10 content using a rabbit polyclonal Api m 10-specific antiserum, as described previously [19]. HSA, human serum albumin; M, molecular weight marker (Figure and supplementary file provided by Blank S. & Grosch J).