Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches.

Chien-Chun Liu,Chih-Chuan Lin,Chien-Hsin Liu,Chen-Hsien You,Jau-Song Yu,Guo-Jen Huang,Po-Jung Wang,Wen-Chin Hsieh,Geoffrey K Isbister

doi:10.1371/journal.pntd.0006138

Abstract

In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom—freeze-dried neurotoxic antivenom (FNAV)—against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two ‘true’ cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.

Highlights

Envenomation through snakebite is an important public health issue in many regions of the world, in tropical countries [1,2,3]
Antivenom therapy is the standard treatment for snakebite
Taiwan has wealth of experience in producing antivenoms, including the bivalent freeze-dried neurotoxic antivenom (FNAV), which is raised against venom proteins from Bungarus multicinctus and Naja atra

Summary

Introduction

Envenomation through snakebite is an important public health issue in many regions of the world, in tropical countries [1,2,3]. Researchers have applied animal models to evaluate the ability of antivenoms to cross-neutralize the venoms of other snakes in the same genus that represent a public health concern [6, 7]. These approaches, combined with immunological and proteomics techniques, have been successfully used to identify specific venom proteins that can be recognized by antivenom [8,9,10,11]. Such information can be used to design a new strategy for improving the immune response of animals against poorly immunogenic antigens or major toxic components so as to further improve the efficacy of antivenoms [12,13,14]

Objectives

Methods

Discussion

Conclusion