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Allergen Encyclopedia
Table of Contents

Whole Allergen

i75 European hornet

i75 European hornet Scientific Information

Type:

Whole Allergen

Display Name:

European hornet

Allergen code:

i75

Family:

Vespidae

Species:

Vespa crabro

Route of Exposure:

Injection of venom

Source Material:

Venom

Latin Name:

Vespa crabro

WHO/ICD-11 code:

XM31U2

(ICD-11 is currently under implementation by WHO and the ICD-11 codes displayed in the encyclopedia may not yet be available in all countries)

Summary

The European hornet (Vespa crabro) is a large vespid wasp native to most of Europe and Asia. It injects venom for self-defense and to capture prey via a stinging apparatus. In Europe, V. crabro is responsible for only occasional vespid venom allergic reactions, but these reactions are likely to be severe and can induce fatal anaphylaxis. Three allergenic molecules have been characterized in V. crabro venom to date, which cross-react to some degree with homologous proteins in venom from other Hymenoptera insects such as yellow jacket (Vespula spp.) and honeybee (Apis mellifera). 

Allergen

Taxonomy    

Taxonomic tree of Vespa crabro (European hornet) (1, 2)

Domain

Eukaryota

Kingdom

Metazoa

Phylum

Arthropoda

Subphylum

Uniramia

Class

Insecta

Order

Hymenoptera

Family

Vespidae

Genus

Vespa.

Tissue

Venom from Hymenoptera insects (hornets, bees, wasps, and ants) contains a range of bioactive toxins and allergenic proteins that can be associated with local and/or systemic allergic reactions including life-threatening anaphylaxis in sensitized individuals (3-5).

Environmental Characteristics

Living environment

V. crabro is considered the largest native vespid wasp in Europe (6), with a body size of approximately 9‒10 mm in length and builds colony nests in the ground or sheltered areas (7). In the northern hemisphere, Hymenoptera stinging events generally occur during late summer or early fall, with peak events occurring in August (8). 

Worldwide distribution 

The European hornet is native to most of Europe and Asia and can also be found in eastern North America (9). 

Route of Exposure

Main

Female Hymenoptera insects have a stinging apparatus at the tail end of their abdominal segment, which is used for self-defense, to repel colony intruders, and to capture prey (5, 6, 10). A sting can deliver between 100 ng and 50 µg of venom (5). V. crabro is not particularly aggressive to humans, and usually only stings when provoked or disturbed.

Clinical Relevance

Hymenoptera stings account for 9‒23% of all systemic allergic reactions, and 20‒40% of all types of  reported each year, making them a major cause of hypersensitivity responses (4). An estimated 50% of subjects who experienced fatal reactions had no documented history of a systemic reaction to Hymenoptera sting (11).

In Europe, V. crabro is responsible for only occasional vespid venom allergic reactions, but these reactions are likely to be severe (12). A case history analysis of 157 Hymenoptera allergic patients in Portugal estimated that the relative risk of a life-threatening reaction was approximately three times higher with V. crabro versus yellow jacket or honeybee (RR=2.74, CI 95%: 1.93‒3.89; R<0.0001) [ANT03]. In this study, the percentage of life-threatening reactions was 81.2% in the V. crabro allergic patients group (n=35), versus 27.8% in the Vespula spp. allergic group (n=97) and 24% in the Apis mellifera allergic group (n=25) (13).

In general, exposure to venom leads to a type I hypersensitivity reaction, with clinical symptoms that can include local burning, persistent local pain, angioedema, generalized urticaria, decreased blood pressure, bronchospasm, cardiac arrest, and respiratory and anaphylactic shock in sensitized individuals (14, 15). Interestingly, in a study of 220 patients allergic to bee, wasp, or European hornet venom, total IgE levels of patients with mild symptoms (e.g. grade I, generalized skin symptoms) were higher than those of patients with either moderate reactions (e.g. grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms) or severe reactions (e.g. grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness) (248.0 kU/l vs 75.2 kU/l vs 56.5 kU/l, respectively; p<0.001) [STU07].

A recent review paper identified 55 detailed cases of Vespa spp. hornet sting in 27 papers, with a mortality rate of 36.4% due mainly to multi-organ failure with common complications of renal failure and liver dysfunction (10).

In a report from Nepal, three subjects developed acute renal failure following multiple hornet stings (species unidentified) and were admitted to hospital; two patients recovered following hemodialysis and treatment and one patient died (8). A case report from Turkey described a 30-year-old male with no history of cardiovascular or systemic abnormalities who developed atrial fibrillation, shortness of breath, dizziness, and headache following a suspected V. crabro sting and recovered fully after emergency treatment with anti-coagulants and intravenous propafenone (16). A further case report from Serbia described a healthy 45-year-old male with no history of ischemic heart disease who developed acute myocardial infarction and anaphylaxis following a V. crabro sting and was admitted to ICU (5). Skin prick tests (SPT) did not confirm sensitivity to bee, wasp, or hornet and total serum IgE levels were normal (5). The patient was treated with coronary vasodilators, antiarrhythmics, anti-aggregation drugs, and sedatives, and discharged from hospital 20 days following the sting event (5).

Prevention and Therapy

Allergen immunotherapy

Immunotherapies for wasp venom aim to increase suppressor cytokines such as IL-10 and TNF-β, and decrease IL-4 secretion (4).

Molecular Aspects

Allergenic molecules

The following allergens and molecular epitopes have been characterized to date from V. crabro venom (17):

Allergen

Type

Mass (kDa)

Vesp c 1

Phospholipase A1

33.3

Vesp c 2

Hyaluronidase

41

Vesp c 5

Unknown venom allergen 5

23

Biomarkers of severity

Vesp c 5, or Antigen 5, has no toxic action but has been frequently reported to be the most allergenic component in different species of social wasps including Vespa spp. (4)

Cross-reactivity

There is a wide potential for cross-reactivity between different species of Hymenoptera due to high structural and antigenic similarity between primary sequences of allergens (4, 9, 18). The three major proteins in V. crabro venom (Vesp c 1, Vesp c 2, and Vesp c 5) are structurally and antigenically related to those from other vespid wasps including Vespula yellow jackets (9, 18).

In Italy, 17 patients with a severe reaction after V. crabro sting showed non discriminative skin/CAP positivity to Vespula spp. (19). In 11/17 of these subjects, Vespula venom completely inhibited IgE binding to V. crabro venom, whereas V. crabro venom only partially (<75%) inhibited IgE binding of Vespula venom (19).

Cross-inhibition tests in 24 consecutive patients who experienced anaphylaxis after a V. crabro sting in Europe showed that 17/24 were sensitized to wasp (Vespula germanica) venom, 2/24 with completely cross-reactive epitopes, 1/24 with only V. crabro venom, and 4/24 with separate epitopes of both venoms (20). These authors concluded that at least 70% of the patients who experienced a systemic allergic reaction to V. crabro were actually allergic to wasp venom (20).

A study in Spain detected IgE antibodies to Polistes dominulus (European paper wasp), Vespula germanica (German wasp), and to a lesser extent V. crabro in a large group of sera from patients sensitized to vespids (21). As only a minority of subjects in this study had co-existing antibodies to two species, the authors suggested that most of the patients were originally sensitized to just one species with additional positivity to other venoms due to cross-reactivity (21).

Antigen 5 (Vesp c 5) is found in different social wasp species (e.g., Vespa, Vespula, Polistes, Dolichovespula, and Polybia spp.) and shows sequence homology with a variety of proteins including ant venom, tomato leaf tobacco, mammalian testis protein, and human brain tumor (4). Vesp c 5 demonstrated sequence identities to Ag5 homologs in venom from Dolichovespula (66.3‒72.1%) and yellow jacket (65.4‒71.6%) (18), but no cross-reactive antigen reactivity with ant venom Ag5 (4).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Christian  Fischer 

 

Last reviewed:April 2022

References
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  2. CABI. Vespa 2022.
  3. Dos Santos-Pinto JRA, Perez-Riverol A, Lasa AM, Palma MS. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms. Toxicon. 2018;148:172-96.
  4. Bazon ML, Silveira LH, Simioni PU, Brochetto-Braga MR. Current Advances in Immunological Studies on the Vespidae Venom Antigen 5: Therapeutic and Prophylaxis to Hypersensitivity Responses. Toxins. 2018;10(8).
  5. Cvetković-Matić D, Asanin M, Matić D, Ivanović B, Simić D, Kalezić N, et al. Acute myocardial infarction following a hornet sting. Vojnosanit Pregl. 2009;66(4):333-7.
  6. Stetsun H, Matushkina NA. Sting morphology of the European hornet, Vespa crabro L., (Hymenoptera: Vespidae) re-examined. Entomological Science. 2020;23(4):416-29.
  7. Kwon O, Choi MB. Interspecific hierarchies from aggressiveness and body size among the invasive alien hornet, Vespa velutina nigrithorax, and five native hornets in South Korea. PLOS ONE. 2020;15(7):e0226934.
  8. Dongol Y, Paudel YP, Shrestha RK, Aryal G. Acute renal failure following multiple hornet stings. Clin Kidney J. 2012;5(2):158-61.
  9. Hoffman DR, Jacobson RS, Zerboni R. Allergens in hymenoptera venom. XIX. Allergy to Vespa crabro, the European hornet. Int Arch Allergy Appl Immunol. 1987;84(1):25-31.
  10. Herrera C, Leza M, Martínez-López E. Diversity of compounds in Vespa spp. venom and the epidemiology of its sting: a global appraisal. Arch Toxicol. 2020;94(11):3609-27.
  11. Bilò MB, Bonifazi F. The natural history and epidemiology of insect venom allergy: clinical implications. Clin Exp Allergy. 2009;39(10):1467-76.
  12. Kosnik M, Korosec P. Importance of basophil activation testing in insect venom allergy. Allergy, Asthma & Clinical Immunology. 2009;5(1):11.
  13. Antonicelli L, Bilò MB, Napoli G, Farabollini B, Bonifazi F. European hornet (Vespa crabro) sting: a new risk factor for life-threatening reaction in hymenoptera allergic patients? Eur Ann Allergy Clin Immunol. 2003;35(6):199-203.
  14. Bazon ML, Silveira LH, Simioni PU, Brochetto-Braga MR. Current Advances in Immunological Studies on the Vespidae Venom Antigen 5: Therapeutic and Prophylaxis to Hypersensitivity Responses. Toxins. 2018;10(8):305.
  15. Bousquet J, Müller UR, Dreborg S, Jarisch R, Malling HJ, Mosbech H, et al. Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology. Allergy. 1987;42(6):401-13.
  16. Okutucu S, Sabanov C, Abdulhayoglu E, Evranos B, Sahiner L, Kaya E, et al. A RARE CAUSE OF ATRIAL FIBRILLATION: EUROPEAN HORNET STING. International Journal of Cardiology - INT J CARDIOL. 2011;147.
  17. allergome.org. Vespa crabro 2021 [cited 2022 20.01.22]. Available from: http://www.allergome.org/script/search_step2.php.
  18. Hoffman DR. Allergens in Hymenoptera venom XXV: The amino acid sequences of antigen 5 molecules and the structural basis of antigenic cross-reactivity. Journal of Allergy and Clinical Immunology. 1993;92(5):707-16.
  19. Severino MG, Caruso B, Bonadonna P, Labardi D, Macchia D, Campi P, et al. Cross reactivity between European Hornet and Yellow Jacket venoms. Journal of Allergy and Clinical Immunology. 2009;123(2):S243.
  20. Kosnik M, Korosec P, Silar M, Music E, Eržen R. Wasp venom is appropriate for immunotherapy of patients with allergic reaction to the European hornet sting. Croatian medical journal. 2002;43:25-7.
  21. Blanca M, Garcia F, Miranda A, Carmona MJ, Garcia J, Fernandez J, et al. Determination of IgE antibodies to Polistes dominulus, Vespula germanica and Vespa crabro in sera of patients allergic to vespids. Allergy. 1991;46(2):109-14