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Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming.
Toxins (Basel). 2021 03 13; 13(3)T

Abstract

Snakebites are a relatively rare medical emergency in Europe. In more than half of the annual cases caused by Vipera ammodytes, Vipera berus, and Vipera aspis, immunotherapy with animal-derived antivenom is indicated. Among eight products recently identified as available against European medically relevant species, only Zagreb antivenom, Viperfav, and ViperaTAb have been used almost exclusively for decades. Zagreb antivenom comprises V. ammodytes-specific F(ab')2 fragments. Viperfav is a polyspecific preparation based on F(ab')2 fragments against V. aspis, V. berus, and V. ammodytes venoms. ViperaTAb contains Fab fragments against the venom of V. berus. In 2014 the production of Zagreb antivenom was discontinued. Additionally, in the period of 2017 to 2018 a shortage of Viperfav occurred. Due to a lack of the product indicated for the treatment of V. ammodytes bites, other antivenoms were implemented into clinical practice without comparative assessment of their eligibility. The aim of our work was to identify a high-quality antivenom that might ensure the successful treatment of V. ammodytes and V. berus bites at the preclinical level. Differentiation between bites from these two species is difficult and unreliable in clinical practice, so the availability of a unique antivenom applicable in the treatment of envenoming caused by both species would be the most advantageous for Southeastern Europe. Zagreb antivenom, Viperfav, and ViperaTAb, as well as Viper venom antitoxin for V. berus envenoming and the in-development Inoserp Europe, which was designed to treat envenoming caused by all medically important European snakes, were comparatively tested for the first time. Emphasis was placed on their physicochemical properties, primarily purity and aggregate content, as well as their in vivo protective efficacies. As Zagreb antivenom is no longer available on the European market, Viperfav is the highest-quality product currently available and the only antivenom whose neutralisation potency against V. ammodytes and V. berus venoms was above regulatory requirements.

Authors+Show Affiliations

Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Centre of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Centre of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000 Ljubljana, Slovenia. Centre for Clinical Physiology, Faculty of Medicine, University of Ljubljana, Zaloška Cesta 4, 1000 Ljubljana, Slovenia.Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000 Ljubljana, Slovenia.Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Centre of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Centre of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33805701

Citation

Kurtović, Tihana, et al. "Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera Ammodytes and Vipera Berus Envenoming." Toxins, vol. 13, no. 3, 2021.
Kurtović T, Lang Balija M, Brvar M, et al. Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming. Toxins (Basel). 2021;13(3).
Kurtović, T., Lang Balija, M., Brvar, M., Dobaja Borak, M., Mateljak Lukačević, S., & Halassy, B. (2021). Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming. Toxins, 13(3). https://doi.org/10.3390/toxins13030211
Kurtović T, et al. Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera Ammodytes and Vipera Berus Envenoming. Toxins (Basel). 2021 03 13;13(3) PubMed PMID: 33805701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming. AU - Kurtović,Tihana, AU - Lang Balija,Maja, AU - Brvar,Miran, AU - Dobaja Borak,Mojca, AU - Mateljak Lukačević,Sanja, AU - Halassy,Beata, Y1 - 2021/03/13/ PY - 2021/02/15/received PY - 2021/03/05/revised PY - 2021/03/10/accepted PY - 2021/4/3/entrez PY - 2021/4/4/pubmed PY - 2021/7/1/medline KW - Vipera ammodytes KW - Vipera berus KW - ViperaTAb KW - Viperfav KW - Zagreb antivenom KW - preclinical efficacy JF - Toxins JO - Toxins (Basel) VL - 13 IS - 3 N2 - Snakebites are a relatively rare medical emergency in Europe. In more than half of the annual cases caused by Vipera ammodytes, Vipera berus, and Vipera aspis, immunotherapy with animal-derived antivenom is indicated. Among eight products recently identified as available against European medically relevant species, only Zagreb antivenom, Viperfav, and ViperaTAb have been used almost exclusively for decades. Zagreb antivenom comprises V. ammodytes-specific F(ab')2 fragments. Viperfav is a polyspecific preparation based on F(ab')2 fragments against V. aspis, V. berus, and V. ammodytes venoms. ViperaTAb contains Fab fragments against the venom of V. berus. In 2014 the production of Zagreb antivenom was discontinued. Additionally, in the period of 2017 to 2018 a shortage of Viperfav occurred. Due to a lack of the product indicated for the treatment of V. ammodytes bites, other antivenoms were implemented into clinical practice without comparative assessment of their eligibility. The aim of our work was to identify a high-quality antivenom that might ensure the successful treatment of V. ammodytes and V. berus bites at the preclinical level. Differentiation between bites from these two species is difficult and unreliable in clinical practice, so the availability of a unique antivenom applicable in the treatment of envenoming caused by both species would be the most advantageous for Southeastern Europe. Zagreb antivenom, Viperfav, and ViperaTAb, as well as Viper venom antitoxin for V. berus envenoming and the in-development Inoserp Europe, which was designed to treat envenoming caused by all medically important European snakes, were comparatively tested for the first time. Emphasis was placed on their physicochemical properties, primarily purity and aggregate content, as well as their in vivo protective efficacies. As Zagreb antivenom is no longer available on the European market, Viperfav is the highest-quality product currently available and the only antivenom whose neutralisation potency against V. ammodytes and V. berus venoms was above regulatory requirements. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/33805701/Comparison_of_Preclinical_Properties_of_Several_Available_Antivenoms_in_the_Search_for_Effective_Treatment_of_Vipera_ammodytes_and_Vipera_berus_Envenoming_ L2 - https://www.mdpi.com/resolver?pii=toxins13030211 DB - PRIME DP - Unbound Medicine ER -