TY  - JOUR
AB  - Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201.
AU  - Grosch, J.
AU  - Eberlein, B.*
AU  - Waldherr, S.*
AU  - Pascal, M.*
AU  - Dorn, B.*
AU  - San Bartolomé, C.*
AU  - De La Roca Pinzón, F.*
AU  - Schiener, M.
AU  - Darsow, U.*
AU  - Biedermann, T.*
AU  - Lidholm, J.*
AU  - Bilò, M.B.*
AU  - Jakob, T.*
AU  - Schmidt-Weber, C.B.
AU  - Blank, S.
C1  - 72529
C2  - 56640
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Comparative assessment of the allergenicity of hyaluronidases from Polistes dominula (Pol d 2), Vespula vulgaris (Ves v 2), and Apis mellifera Venom (Api m 2).
JO  - Toxins
VL  - 16
IS  - 11
PB  - Mdpi
PY  - 2024
ER  - 

TY  - JOUR
AB  - Nature abounds with an unprecedented diversity of biomolecular innovation [...].
AU  - Lüddecke, T.*
AU  - Blank, S.
C1  - 70389
C2  - 55535
TI  - Animal toxins: Biodiscovery, mechanistic insights and translational potential.
JO  - Toxins
VL  - 16
IS  - 3
PY  - 2024
ER  - 

TY  - JOUR
AB  - Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy.
AU  - Grosch, J.
AU  - Lesur, A.*
AU  - Kler, S.*
AU  - Bernardin, F.*
AU  - Dittmar, G.*
AU  - Francescato, E.*
AU  - Hewings, S.J.*
AU  - Jakwerth, C.A.
AU  - Zissler, U.M.
AU  - Heath, M.D.*
AU  - Ollert, M.*
AU  - Kramer, M.F.*
AU  - Hilger, C.*
AU  - Bilò, M.B.*
AU  - Schmidt-Weber, C.B.
AU  - Blank, S.
C1  - 64885
C2  - 52580
TI  - Allergen content of therapeutic preparations for allergen-specific immunotherapy of European paper wasp venom allergy.
JO  - Toxins
VL  - 14
IS  - 4
PY  - 2022
ER  - 

TY  - JOUR
AB  - 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.
AU  - Feindor, M.*
AU  - Heath, M.D.*
AU  - Hewings, S.J.*
AU  - Carreno Velazquez, T.L.*
AU  - Blank, S.
AU  - Grosch, J.
AU  - Jakob, T.*
AU  - Schmid-Grendelmeier, P.*
AU  - Klimek, L.*
AU  - Golden, D.B.K.*
AU  - Skinner, M.A.*
AU  - Kramer, M.F.*
C1  - 62987
C2  - 51181
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Venom immunotherapy: From proteins to product to patient protection.
JO  - Toxins
VL  - 13
IS  - 9
PB  - Mdpi
PY  - 2021
ER  - 

TY  - JOUR
AB  - Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species’ sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom—immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)—were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20–40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.
AU  - Grosch, J.
AU  - Eberlein, B.*
AU  - Waldherr, S.*
AU  - Pascal, M.*
AU  - Bartolomé, C.S.*
AU  - De La Roca Pinzón, F.*
AU  - Dittmar, M.
AU  - Hilger, C.*
AU  - Ollert, M.*
AU  - Biedermann, T.*
AU  - Darsow, U.*
AU  - Bilò, M.B.*
AU  - Schmidt-Weber, C.B.
AU  - Blank, S.
C1  - 62827
C2  - 51083
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Characterization of new allergens from the venom of the european paper wasp Polistes dominula.
JO  - Toxins
VL  - 13
IS  - 8
PB  - Mdpi
PY  - 2021
ER  - 

TY  - JOUR
AB  - Allergic reactions to stings of Hymenoptera species can have serious or even fatal consequences. If the identification of the culprit insect is possible, venom-specific immunotherapy effectively cures Hymenoptera venom allergies. Although component-resolved diagnostics has strongly evolved in recent years, the differentiation between allergies to closely related species such asPolistes dominulaandVespulaspp. is still challenging. In order to generate the basis for new diagnostic and therapeutic strategies, this study aims at resolving the venom proteomes (venomes) of these species. The venoms ofP. dominulaandVespulaspp. (V. germanica,V. vulgaris) were analyzed by liquid chromatography-mass spectrometry. Resulting proteins were characterized regarding their function, localization and biochemical properties. The analyses yielded 157 proteins inVespulaspp. and 100 inP. dominulavenom; 48 proteins, including annotated allergens, were found in both samples. In addition to a variety of venom trace molecules, new allergen candidates such as icarapin-like protein and phospholipase A2 were identified. This study elucidates the venomes of closely related allergy-eliciting Hymenoptera species. The data indicates that relying on marker allergens to differentiate betweenP. dominulaandVespulaspp. venom allergy is probably insufficient and that strategies using cross-reactive major allergens could be more promising.
AU  - Grosch, J.
AU  - Hilger, C.*
AU  - Bilò, M.B.*
AU  - Kler, S.*
AU  - Schiener, M.
AU  - Dittmar, G.*
AU  - Bernardin, F.*
AU  - Lesur, A.*
AU  - Ollert, M.*
AU  - Schmidt-Weber, C.B.
AU  - Blank, S.
C1  - 59204
C2  - 48702
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Shedding light on the venom proteomes of the allergy-relevant Hymenoptera Polistes dominula (European paper wasp) and Vespula spp. (yellow jacket).
JO  - Toxins
VL  - 12
IS  - 5
PB  - Mdpi
PY  - 2020
ER  - 

TY  - JOUR
AB  - Haemolysin BL is an important virulence factor regarding the diarrheal type of food poisoning caused by Bacillus cereus. However, the pathogenic importance of this three-component enterotoxin is difficult to access, as nearly all natural B. cereus culture supernatants additionally contain the highly cytotoxic Nhe, the second three-component toxin involved in the aetiology of B. cereus-induced food-borne diseases. To better address the toxic properties of the Hbl complex, a system for overexpression and purification of functional, cytotoxic, recombinant (r)Hbl components L₂, L₁ and B from E. coli was established and an nheABC deletion mutant was constructed from B. cereus reference strain F837/76. Furthermore, 35 hybridoma cell lines producing monoclonal antibodies (mAbs) against Hbl L₂, L₁ and B were generated. While mAbs 1H9 and 1D8 neutralized Hbl toxicity and thus, represent important tools for future investigations of the mode-of-action of Hbl on the target cell surface, mAb 1D7, in contrast, even enhanced Hbl toxicity by supporting the binding of Hbl B to the cell surface. By using the specific mAbs in Dot blots, indirect and hybrid sandwich enzyme immuno assays (EIAs), complex formation between Hbl L₁ and B, as well as L₁ and L₂ in solution could be shown for the first time. Surface plasmon resonance experiments with the rHbl components confirmed these results with KD values of 4.7 × 10(-7) M and 1.5 × 10(-7) M, respectively. These findings together with the newly created tools lay the foundation for the detailed elucidation of the molecular mode-of-action of the highly complex three-component Hbl toxin.
AU  - Tausch, F.*
AU  - Dietrich, R.*
AU  - Schauer, K.*
AU  - Janowski, R.
AU  - Niessing, D.
AU  - Märtlbauer, E.*
AU  - Jessberger, N.*
C1  - 51947
C2  - 43603
CY  - Basel
TI  - Evidence for complex formation of the Bacillus cereus haemolysin BL components in solution.
JO  - Toxins
VL  - 9
IS  - 9
PB  - Mdpi Ag
PY  - 2017
ER  - 

TY  - JOUR
AB  - Increasing frequencies of 3-acetyl-deoxynivalenol (3-ADON)-producing strains of Fusarium graminearum (3-ADON chemotype) have been reported in North America and Asia. 3-ADON is nearly nontoxic at the level of the ribosomal target and has to be deacetylated to cause inhibition of protein biosynthesis. Plant cells can efficiently remove the acetyl groups of 3-ADON, but the underlying genes are yet unknown. We therefore performed a study of the family of candidate carboxylesterases (CXE) genes of the monocot model plant Brachypodium distachyon. We report the identification and characterization of the first plant enzymes responsible for deacetylation of trichothecene toxins. The product of the BdCXE29 gene efficiently deacetylates T-2 toxin to HT-2 toxin, NX-2 to NX-3, both 3-ADON and 15-acetyl-deoxynivalenol (15-ADON) into deoxynivalenol and, to a lesser degree, also fusarenon X into nivalenol. The BdCXE52 esterase showed lower activity than BdCXE29 when expressed in yeast and accepts 3-ADON, NX-2, 15-ADON and, to a limited extent, fusarenon X as substrates. Expression of these Brachypodium genes in yeast increases the toxicity of 3-ADON, suggesting that highly similar genes existing in crop plants may act as susceptibility factors in Fusarium head blight disease.
AU  - Schmeitzl, C.*
AU  - Varga, E.*
AU  - Warth, B.*
AU  - Kugler, K.G.
AU  - Malachová, A.*
AU  - Michlmayr, H.*
AU  - Wiesenberger, G.*
AU  - Mayer, K.F.X.
AU  - Mewes, H.-W.*
AU  - Krska, R.*
AU  - Schuhmacher, R.*
AU  - Berthiller, F.*
AU  - Adam, G.*
C1  - 47603
C2  - 39433
CY  - Basel
TI  - Identification and characterization of carboxylesterases from Brachypodium distachyon deacetylating trichothecene mycotoxins.
JO  - Toxins
VL  - 8
IS  - 1
PB  - Mdpi Ag
PY  - 2016
ER  -