Abstract
Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89–6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61–2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity.
Highlights
Snakebite envenomation constitutes a highly relevant public health problem with worldwide annual mortality estimated to be at least 20,000, the exact death figure could soar as high as 94,000 yearly [1]
The venom of Thai Naja kaouthia (Nk-T) was resolved by cation-exchange chromatography into eight peaks, five of which constituted the majority of proteins in the venom (Figure 1a)
Cobra venoms are highly toxic due to the effects of rapid neuromuscular paralysis and extensive tissue necrosis [2,17]. These complications are mainly attributed to the two largest protein families, i.e., three-finger toxins (3FTxs) and phospholipase A2 s (PLA2 s), which are the major constituents of most cobra venoms [18]
Summary
Snakebite envenomation constitutes a highly relevant public health problem with worldwide annual mortality estimated to be at least 20,000, the exact death figure could soar as high as 94,000 yearly [1]. Snakebite envenomation is a medical emergency needing specialized treatment in which antivenom remains the only proven and accepted antidote for use [2]. Antivenom is derived from animal immunoglobulins (commonly from horses or mules) and acts by forming immunocomplexes with toxins, thereby rendering them biologically inactive. Good-quality antivenom, when used appropriately, can effectively reduce the mortality and morbidity associated with snakebite envenomation [3]. Antivenom is included in the World Health Organization (WHO) Model. List of Essential Medicine and is expected to be available in countries affected by snakebites, typically in the tropics and subtropics. Unlike most drugs for other tropical diseases that can be Toxins 2016, 8, 86; doi:10.3390/toxins8040086 www.mdpi.com/journal/toxins
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