Preclinical Assessment of a New Polyvalent Antivenom (Inoserp Europe) against Several Species of the Subfamily Viperinae

Abstract

The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is indicated for patients with systemic envenoming, of which there are approximately 4000 annual cases in Europe, and was suggested as an indication for young children and pregnant women, even if they do not have systemic symptoms. In the present study, the safety and venom-neutralizing efficacy of Inoserp Europe—a new F(ab’)2 polyvalent antivenom, designed to treat envenoming by snakes in the Eurasian region—were evaluated. In accordance with World Health Organization recommendations, several quality control parameters were applied to evaluate the safety of this antivenom. The venom-neutralizing efficacy of the antivenom was evaluated in mice and the results showed it had appropriate neutralizing potency against the venoms of several species of Vipera, Montivipera, and Macrovipera. Paraspecificity of the antivenom was demonstrated as well, since it neutralized venoms of species not included in the immunization schemes and contains satisfactory levels of total proteins and F(ab’)2 fragment concentration. Therefore, this new polyvalent antivenom could be effective in the treatment of snake envenoming in Europe, including Western Russia and Turkey.

Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming

“…Further precautionary investigation should be considered since precipitation and/or aggregation might indicate loss of activity and an increased risk of adverse reactions [ 20 ]. When reconstituted with water for injection, lyophilised Inoserp Europe produced a pale yellow, transparent solution, as already reported [ 17 ].…”

“…Further precautionary investigation should be considered since precipitation and/or aggregation might indicate loss of activity and an increased risk of adverse reactions [20]. When reconstituted with water for injection, lyophilised Inoserp Europe produced a pale yellow, transparent solution, as already reported [17]. a Expressed as R or number of median lethal doses (LD50) of venom that can be neutralised in vivo by one mL of antivenom; b ELISA unit; c arbitrary unit; d for full list see [17].…”

“… a Expressed as R or number of median lethal doses (LD 50 ) of venom that can be neutralised in vivo by one mL of antivenom; b ELISA unit; c arbitrary unit; d for full list see [ 17 ]. …”

“…Our study covered one additional antivenom as a potential candidate, Viper venom antitoxin (Poland), which was selected as the representative most similar to ViperaTAb concerning specificity, but much less present on the market and almost completely devoid of literature data associated with its biochemical and functional properties. Finally, a new product in development, the polyvalent antivenom Inoserp Europe (Mexico), which is designed to treat envenoming caused by all medically important European snakes but is not yet available on the market [ 17 ], was also comparatively evaluated.…”

Snakebite Envenoming Diagnosis and Diagnostics

“…Despite the close phylogenetic relationship between Vipera spp., inter-and intraspecific venom variability might occur, both with regard to the toxins present and their individual abundances, which, in turn, may affect antivenom efficacy (213,(229)(230)(231). However, available monospecific antivenoms may still show cross-reactivity between venoms, and studies have shown that antivenom raised against venom from one species can, in some cases, have clinical efficacy against venoms from other vipers indigenous to Europe (214,215,232).…”