Venomics of Naja sputatrix , the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization

Tan, Nget Hong; Wong, Kin Ying; Tan, Choo Hock

doi:10.1016/j.jprot.2017.01.018

Cited by 80 publications

(73 citation statements)

References 48 publications

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“…The implication follows that high amounts of antivenom protein may be needed to treat a snakebite, with heterologous protein loads reaching as much as 15 g/treatment for some antivenoms in severe envenoming cases 7 . Particularly, elapid antivenoms often have an unbalanced antibody content with relatively low amounts of antibodies against small neurotoxic venom components that have low immunogenicity, which often leads to low immune responses in production animals 8 – 10 . Despite the maturity of immunotherapy, there remains a need for cost-effective antivenoms with improved safety and efficacy 5 .…”

Section: Introductionmentioning

confidence: 99%

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

et al. 2018

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The black mamba (Dendroaspis polylepis) is one of the most feared snake species of the African savanna. It has a potent, fast-acting neurotoxic venom comprised of dendrotoxins and α-neurotoxins associated with high fatality in untreated victims. Current antivenoms are both scarce on the African continent and present a number of drawbacks as they are derived from the plasma of hyper-immunized large mammals. Here, we describe the development of an experimental recombinant antivenom by a combined toxicovenomics and phage display approach. The recombinant antivenom is based on a cocktail of fully human immunoglobulin G (IgG) monoclonal antibodies capable of neutralizing dendrotoxin-mediated neurotoxicity of black mamba whole venom in a rodent model. Our results show the potential use of fully human monoclonal IgGs against animal toxins and the first use of oligoclonal human IgG mixtures against experimental snakebite envenoming.

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Section: Introductionmentioning

confidence: 99%

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

et al. 2018

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“…These approaches, combined with immunological and proteomics techniques, have been successfully used to identify specific venom proteins that can be recognized by antivenom [ 8 – 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 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Antivenoms against a number of scorpion venoms have been reported, but the potency of antivenom in relation to the potency of scorpion venom and both LD 50 and ED 50 should be determined paradoxically and canonically . The LD 50 s of intravenous venom from Vipera berus berus (0.4 μg/kg; symptoms included head‐drop, floppy neck, flaccid paralysis of limb, respiratory paralysis, and death), Laticauda colubrine (0.05‐0.13 μg/g), Sri Lankan Bungarus caeruleus (0.07 μg/g), Naja sputatrix and A. australis (0.5 ng) show that the scorpion venoms are highly toxic. Similar symptoms were observed for Vipera nikolskii venom (1.0 μg/kg), but the symptoms, caused by phospholipase A 2 , were lost after the mice were injected with strontium .…”

Section: Discussionmentioning

confidence: 99%

Determination of median effective dose (ED₅₀) of scorpion antivenom against scorpion envenomation using a newly developed formula

Saganuwan

2018

Anim Models and Exp Med

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Background About 50 species of scorpions cause fatal scorpionism worldwide. Most of these are members of the Buthidae family, and include, among others, Mesobuthus eupeus , Androctonus crassicauda , Leiurus abdullahbayrami , Leiurus quinquestriatus , Tityus pachyurus and Androctonus australis . Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments. Methods In view of this, a literature search was carried out with the aim of modifying the formula ( ) for calculation of the median lethal dose (LD 50 ) of scorpion venom and the ED 50 of antivenom. The human equivalent dose (HED) formula was assessed for extrapolation of LD 50 and ED 50 from animals to human for comparison and relevance with the new formula. Results The findings showed that the newly developed formula (LD 50 = ED 50 1/3 × W a × 10 −4 ) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD 50 and ED 50 values for scorpion venom and antivenom, respectively. Conclusion The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement (3Rs).

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Venomics of Naja sputatrix , the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization

Cited by 80 publications

References 48 publications

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

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

Determination of median effective dose (ED₅₀) of scorpion antivenom against scorpion envenomation using a newly developed formula

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Venomics of Naja sputatrix , the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization

Cited by 80 publications

References 48 publications

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

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

Determination of median effective dose (ED50) of scorpion antivenom against scorpion envenomation using a newly developed formula

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Determination of median effective dose (ED₅₀) of scorpion antivenom against scorpion envenomation using a newly developed formula