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

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.

A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms

“…Thus the pan-specific PDAV could offer broad cross neutralization of venoms from different and geographically separated snakes and could benefit a large number of snakebite victims. The rationale of the novel immunization strategy was discussed previously (83). The result of this study is a proof of concept of the 'diverse toxin repertoire' immunization strategy in the production of pan-specific antivenom against neurotoxic venoms.…”

“…To further test the concept of the 'diverse toxin repertoire' immunization strategy, we assayed the ability of the panspecific PDAV to inhibit the venoms of a variety of elapids from different continents. It was shown that the pan-specific PDAV could effectively neutralize at least 36 neurotoxic venoms of 10 genera and from 4 continents including sea snakes from both Australia and the Arabian Sea (83).…”

A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus)

“…There are several suggestions to revolutionize antivenom production, e.g., the development of recombinant antivenom [ 73 ], development of elapid antivenom by immunizing horses with recombinant consensus short-chain α-neurotoxins [ 74 ], and re-formulation of toxin-targeting, pan-species antivenom [ 75 , 76 ]. These new initiatives are, however, challenging in terms of practicality owing to the enormous time and cost needed in R&D, various regulatory constraints, limited market size, and low-profit margin of the product.…”

De Novo Venom-Gland Transcriptomics of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia—Next-Generation Sequencing, Functional Annotation and Toxinological Correlation

“…Hence, antivenom manufacturers should ensure that the product contains adequate antibodies that are sufficiently immunoreactive toward both types of neurotoxins, so that the reversal of neurotoxicity caused by either SNTX or LNTX can be effective. The production of antivenom toward specific toxin targets can be improved through recent innovations of recombinant technologies [ 41 , 42 ] and re-formulation of specific toxin-targeting antivenom [ 43 , 44 ] to achieve higher potency against the different toxins.…”