Third generation antivenomics: Pushing the limits of the in vitro preclinical assessment of antivenoms

D Pla,Y Rodríguez,J.J Calvete

doi:10.1016/j.toxicon.2018.06.002

Abstract

Second generation antivenomics is a translational venomics approach designed to complement in vivo preclinical neutralization assays. It provides qualitative and quantitative information on the set of homologous and heterologous venom proteins presenting antivenom-recognized epitopes and those exhibiting impaired immunoreactivity. In a situation of worrying antivenom shortage in many tropical and sub-tropical regions with high snakebite mortality and morbidity rates, such knowledge has the potential to facilitate the optimal deployment of currently existing antivenoms and to aid in the rational design of novel broad specificity antidotes. The aim of the present work was to expand the analytical capability of the immunoaffinity second-generation antivenomics platform, endowing it with the ability to determine the maximal binding capacity of an antivenom toward the different toxins present in a venom, and to quantify the fraction of venom-specific antibodies present in a given antivenom. The application of this new platform, termed third generation (3G) antivenomics, in the preclinical evaluation of antivenoms is illustrated in this paper for the case of antivenom EchiTAb-Plus-ICP® reactivity towards the toxins of homologous (B. arietans) and heterologous (N. melanoleuca) venoms.

Highlights

Snakebite envenoming is an occupational and environmental disease that annually kills over95,000 people residing in some of the world’s most disadvantaged rural communities of tropical and sub-tropical developing countries in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, and that leaves over 300,000 surviving victims with permanent physical disabilities [1,2,3].The scale of this problem may be far greater than suggested by statistics from hospital-based care.In addition to representing a significant cause of death, snakebite contributes to a depressing cycle of poverty in the world’s most vulnerable communities [4,5]
The binding capacity of EchiTAb-Plus-ICP® toward the different toxins present in the venom of B. arietans from Ghana was assessed by incubating identical affinity chromatographic columns with increasing amounts of venom until saturation was reached
Antivenomics isistranslational translational venomics applied the functional characterization of Antivenomics venomics applied for the for functional characterization of antivenoms

Summary

Introduction

Snakebite envenoming is an occupational and environmental disease that annually kills over95,000 people residing in some of the world’s most disadvantaged rural communities of tropical and sub-tropical developing countries in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, and that leaves over 300,000 surviving victims with permanent physical disabilities [1,2,3].The scale of this problem may be far greater than suggested by statistics from hospital-based care.In addition to representing a significant cause of death, snakebite contributes to a depressing cycle of poverty in the world’s most vulnerable communities [4,5]. 95,000 people residing in some of the world’s most disadvantaged rural communities of tropical and sub-tropical developing countries in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, and that leaves over 300,000 surviving victims with permanent physical disabilities [1,2,3]. The scale of this problem may be far greater than suggested by statistics from hospital-based care.

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