A pan-specific antiserum produced by a novel immunization strategy shows a high spectrum of neutralization against neurotoxic snake venoms

Kavi Ratanabanangkoon,Kae Yi Tan,Kritsada Pruksaphon,José María Gutiérrez,Chaiya Klinpayom,Naeem H Quraishi,Choo Hock Tan

doi:10.1038/s41598-020-66657-8

Abstract

Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. Snake antivenoms are mostly effective against the venoms used in their production. It is thus crucial that effective and affordable antivenom(s) with wide para-specificity, capable of neutralizing the venoms of a large number of snakes, be produced. Here we studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a ‘diverse toxin repertoire’ consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species. This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. We now show that the antiserum can neutralize 9 out of 10 additional neurotoxic venoms. Altogether, 36 snake venoms belonging to 10 genera from 4 continents were neutralized by the antiserum. Toxin profiles previously generated using proteomic techniques of these 36 venoms identified α-neurotoxins, β-neurotoxins, and cytotoxins as predominant toxins presumably neutralized by the antiserum. The bases for the wide para-specificity of the antiserum are discussed. These findings indicate that it is feasible to generate antivenoms of wide para-specificity against elapid neurotoxic venoms from different regions in the world and raises the possibility of a universal neurotoxic antivenom. This should reduce the mortality resulting from neurotoxic snakebite envenomation.

Highlights

Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms
These toxin fractions contained all the toxic components of the venoms, mostly presynaptic and postsynaptic neurotoxins and cytotoxins, but were devoid of the high molecular mass, highly immunogenic non-toxic proteins[11,12]. This antiserum neutralizes over two dozen homologous /heterologous elapid venoms of snakes inhabiting Asia and Africa[11]. We demonstrated that this pan-specific antiserum neutralized nine additional neurotoxic venoms of elapids from Central America, Africa, and Australia, including sea snakes and sea kraits
Other venoms tested include those of the tiger snake (Notechis scutatus), the king brown snake (Pseudechis australis) and the coastal taipan (Oxyuranus scutellatus), which are classified within WHO Category 1 most medically important snakes from Australia and Papua New Guinea

Summary

Introduction

Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. We studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a ‘diverse toxin repertoire’ consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. Pan-specific antivenoms with wide para specificity can be useful in cases where the culprit snake is not identified or captured, and species identification of the snake cannot be made In this context, we have previously produced an experimental pan-specific equine antiserum that is capable of neutralizing 27 neurotoxic venoms from homologous and heterologous snake species inhabiting Asia and Africa. Specimens) possible basis for the wide para-specificity observed, and its potential application for the preparation of ‘universal neurotoxic antivenom’ are proposed

Methods

Results

Conclusion