Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15404

Special Issue Editor


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Guest Editor
Center of Allergy and Environment (ZAUM), Technical University of Munich, Faculty of Medicine and Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Munich, Germany
Interests: hymenoptera venom; venom allergy; allergy; immunological mechanisms; T cell response; B cell response; antibodies; immunological tolerance; allergen; venom proteomics; biochemical protein characterization
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Special Issue Information

Dear Colleagues,

I am pleased to invite you to contribute to this Special Issue of Toxins dealing with all aspects of venom allergy. Venom allergy is one of the most serious IgE-mediated hypersensitivity reactions due to the high risk of severe and even fatal anaphylaxis. In different regions of the world, stings of various Hymenoptera species, such as bees, yellow jackets, wasps or stinging ants, are common elicitors of venom allergy. Moreover, invasive species, such as the European paper wasp or the Asian hornet, are gaining importance in allergology. In the majority of patients, venom allergy can be effectively treated by venom-specific immunotherapy, the only available immunomodulatory and curative approach. However, adequate patient management and treatment rely on a comprehensive diagnostic work-up, including the proof of clinically relevant sensitization and identification of the allergy-relevant venom. In recent years, biochemical and molecular biological methods have made a significant contribution to the identification and characterization of new allergens of Hymenoptera venoms, shifting the focus from the whole venom to individual allergenic molecules. For instance, this has led to the development of molecular or component-resolved diagnostics, which in several cases has improved accurate diagnosis. Moreover, venom allergy represents an ideal model to study the mechanisms of allergic inflammation and immune tolerance to allergens as well as the allergen–immune system interaction.

This Special Issue aims to give a comprehensive overview of current state-of-the-art concepts, as well as the latest developments and further perspectives, in venom allergy. Moreover, allergy-relevant species, as well as their venoms and venom allergens, should be addressed.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) venom proteomics and allergens, diagnosis and treatment of venom allergy as well as basic immunological and biochemical mechanisms.

I look forward to receiving your contributions.

Dr. Simon Blank
Guest Editor

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Keywords

  • allergen
  • allergy diagnosis
  • Hymenoptera venom
  • immunological tolerance
  • insect sting anaphylaxis
  • stinging Hymenoptera
  • venom allergy
  • venom–immune system interaction
  • venom proteomics
  • venom-specific immunotherapy

Published Papers (5 papers)

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Research

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13 pages, 2825 KiB  
Article
Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy
by Johannes Grosch, Antoine Lesur, Stéphanie Kler, François Bernardin, Gunnar Dittmar, Elisabetta Francescato, Simon J. Hewings, Constanze A. Jakwerth, Ulrich M. Zissler, Matthew D. Heath, Markus Ollert, Matthias F. Kramer, Christiane Hilger, Maria Beatrice Bilò, Carsten B. Schmidt-Weber and Simon Blank
Toxins 2022, 14(4), 284; https://doi.org/10.3390/toxins14040284 - 15 Apr 2022
Cited by 6 | Viewed by 3238
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment)
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15 pages, 2442 KiB  
Article
Biological and Inflammatory Effects of Antigen 5 from Polybia paulista (Hymenoptera, Vespidae) Venom in Mouse Intraperitoneal Macrophages
by Murilo Luiz Bazon, Luis Gustavo Romani Fernandes, Isabela Oliveira Sandrini Assugeni, Lucas Machado Pinto, Patrícia Ucelli Simioni, Ricardo de Lima Zollner and Márcia Regina Brochetto Braga
Toxins 2021, 13(12), 850; https://doi.org/10.3390/toxins13120850 - 29 Nov 2021
Cited by 1 | Viewed by 2115
Abstract
The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen [...] Read more.
The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen 5 from P. paulista venom, expressed recombinantly (rPoly p 5), on BALB/c mice peritoneal macrophages, activated or not with LPS, was assessed. Here, we analyzed cell viability changes, expression of the phosphorylated form of p65 NF-κB subunit, nitric oxide (NO), proinflammatory cytokines production, and co-stimulatory molecules (CD80, CD86). The results suggest that rPoly p 5 does not affect NO production nor the expression of co-stimulatory molecules in mouse peritoneal macrophages. On the other hand, rPoly p 5 induced an increase in IL-1β production in non-activated macrophages and a reduction in the production of TNF-α and MCP-1 cytokines in activated macrophages. rPoly p 5 decreased the in vitro production of the phosphorylated p65 NF-κB subunit in non-activated macrophages. These findings suggest an essential role of this allergen in the polarization of functional M2 macrophage phenotypes, when analyzed in previously activated macrophages. Further investigations, mainly in in vivo studies, should be conducted to elucidate Polybia paulista Ag5 biological role in the macrophage functional profile modulation. Full article
(This article belongs to the Special Issue Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment)
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15 pages, 1559 KiB  
Article
Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula
by Johannes Grosch, Bernadette Eberlein, Sebastian Waldherr, Mariona Pascal, Clara San Bartolomé, Federico De La Roca Pinzón, Michael Dittmar, Christiane Hilger, Markus Ollert, Tilo Biedermann, Ulf Darsow, Maria Beatrice Bilò, Carsten B. Schmidt-Weber and Simon Blank
Toxins 2021, 13(8), 559; https://doi.org/10.3390/toxins13080559 - 10 Aug 2021
Cited by 8 | Viewed by 2720
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment)
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Review

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13 pages, 1349 KiB  
Review
Management of Double Sensitization to Vespids in Europe
by Berta Ruiz-Leon, Pilar Serrano, Carmen Vidal and Carmen Moreno-Aguilar
Toxins 2022, 14(2), 126; https://doi.org/10.3390/toxins14020126 - 8 Feb 2022
Cited by 8 | Viewed by 1708
Abstract
Wasp allergy with a diagnostic profile of double sensitizations to vespid venom is a frequent clinical problem in areas where different genera of wasps are present. Identification of the insect responsible for serious reactions poses a diagnostic challenge as the only effective treatment [...] Read more.
Wasp allergy with a diagnostic profile of double sensitizations to vespid venom is a frequent clinical problem in areas where different genera of wasps are present. Identification of the insect responsible for serious reactions poses a diagnostic challenge as the only effective treatment to date is immunotherapy based on the specific venom. In southern Europe, the double sensitization to Vespula and Polistes venoms is highly frequent. It has been shown that the major allergenic proteins (Phospholipase A1 and Antigen 5) share sequences across the different genera and species, which would be the cause of cross-reactivity. Additionally, the minor allergens (Dipeptidyl-peptidases, Vitellogenins) have been found to share partial sequence identity. Furthermore, venom contains other homologous proteins whose allergenic nature still remains to be clarified. The traditional diagnostic tools available are insufficient to discriminate between allergy to Vespula and Polistes in a high number of cases. IgE inhibition is the technique that best identifies the cross-reactivity. When a double sensitization has indeed been shown to exist or great uncertainty surrounds the primary sensitization, therapy with two venoms is advisable to guarantee the safety of the patient. In this case, a strategy involving alternate administration that combines effectiveness with efficiency is possible. Full article
(This article belongs to the Special Issue Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment)
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17 pages, 746 KiB  
Review
Venom Immunotherapy: From Proteins to Product to Patient Protection
by Martin Feindor, Matthew D. Heath, Simon J. Hewings, Thalia L. Carreno Velazquez, Simon Blank, Johannes Grosch, Thilo Jakob, Peter Schmid-Grendelmeier, Ludger Klimek, David B. K. Golden, Murray A. Skinner and Matthias F. Kramer
Toxins 2021, 13(9), 616; https://doi.org/10.3390/toxins13090616 - 1 Sep 2021
Cited by 6 | Viewed by 4271
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venom Allergy: General Concepts, Allergens, Diagnosis and Treatment)
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