Assessing the preclinical efficacy of antivenoms: from the lethality neutralization assay to antivenomics

Abstract

The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms is the gold standard in the preclinical analysis of antivenom efficacy, and is routinely performed by manufacturers and quality control laboratories. However, the complexity of snake venom composition and toxicological profile demands that, for many venoms, such as those of viperid snakes and some elapids, the neutralization of lethality be complemented with the analysis of the neutralization of other relevant toxic activities, such as hemorrhagic, myotoxic, necrotizing, procoagulant and defibrinogenating effects. This expanded protocol for preclinical testing of antivenoms should be used when a new antivenom is developed or when an existing antivenom is introduced in a new geographical setting for the neutralization of either homologous or heterologous venoms. In recent years, the assessment of the immunological reactivity of antivenoms has been enriched by the use of proteomic tools, with a methodology named 'antivenomics'. This allows the identification of venom components to which antivenoms have, or lack, antibodies, and thus complements the data gathered in neutralization tests, paving the way for a knowledge-based improvement of antivenom design and efficacy. International projects involving participants of manufacturing, quality control and academic research groups should be promoted in order to gain a deeper understanding on the preclinical neutralizing spectrum of antivenoms.