Discovery of human antibodies against forest cobra toxins

Line Ledsgaard Jensen, Mia Øhlenschlæger, Aneesh Karatt-­Vellatt, Mikael Rørdam Andersen, Robert Harrison, Nicholas Casewell, John McCafferty, Andreas Hougaard Laustsen

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Snakebite envenoming is one of the world’s most neglected diseases and it constitutes a serious global health challenge in tropical regions of the world. Each year, snakebite envenoming has a death toll of 125,000 and causes 400,000 amputations. The only effective therapy is antivenom (purified IgGs from venom-immunized horses/sheep), which is often associated with severe adverse reactions to the i.v. administration of large volumes of equine/ovine IgGs. The forest cobra, N. melanoleuca, is the largest cobra species in Africa and of high medical relevance according to the World Health Organization. N. melanoleuca venom derives its toxicity from potent type I and II α-neurotoxins that target nicotinic acetylcholine receptors, causing inhibition of neuromuscular transmission. This inhibition manifests itself clinically as descending neuromuscular paralysis. Here, we report the most recent results of our ongoing work aiming at identifying human antibodies with neutralizing effects against the medically most important toxins from N. melanoleuca venom. Using phage display selection, we discovered a range of different human scFv antibodies from the IONTAS phage display library. These antibodies are currently undergoing further assessment (binding capacity and cross-reactivity to other toxins) with the aim of converting the most promising candidates into the fully human IgG format for preclinical studies. We hope that this work will help pave the way for the first recombinant snakebite antivenom based on oligoclonal mixtures of human IgG antibodies targeting medically relevant toxins from African elapid snake species.
Original languageEnglish
Article number170
JournalToxicon
Volume158
Issue numberSuppl. 1
Pages (from-to)S51-S52
Number of pages2
ISSN0041-0101
DOIs
Publication statusPublished - 2019

Cite this

Jensen, L. L., Øhlenschlæger, M., Karatt-­Vellatt, A., Andersen, M. R., Harrison, R., Casewell, N., ... Laustsen, A. H. (2019). Discovery of human antibodies against forest cobra toxins. Toxicon, 158(Suppl. 1), S51-S52. [170]. https://doi.org/10.1016/j.toxicon.2018.10.179
Jensen, Line Ledsgaard ; Øhlenschlæger, Mia ; Karatt-­Vellatt, Aneesh ; Andersen, Mikael Rørdam ; Harrison, Robert ; Casewell, Nicholas ; McCafferty, John ; Laustsen, Andreas Hougaard. / Discovery of human antibodies against forest cobra toxins. In: Toxicon. 2019 ; Vol. 158, No. Suppl. 1. pp. S51-S52.
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Jensen, LL, Øhlenschlæger, M, Karatt-­Vellatt, A, Andersen, MR, Harrison, R, Casewell, N, McCafferty, J & Laustsen, AH 2019, 'Discovery of human antibodies against forest cobra toxins', Toxicon, vol. 158, no. Suppl. 1, 170, pp. S51-S52. https://doi.org/10.1016/j.toxicon.2018.10.179

Discovery of human antibodies against forest cobra toxins. / Jensen, Line Ledsgaard; Øhlenschlæger, Mia ; Karatt-­Vellatt, Aneesh; Andersen, Mikael Rørdam; Harrison, Robert; Casewell, Nicholas; McCafferty, John; Laustsen, Andreas Hougaard.

In: Toxicon, Vol. 158, No. Suppl. 1, 170, 2019, p. S51-S52.

Research output: Contribution to journalConference abstract in journalResearchpeer-review

TY - ABST

T1 - Discovery of human antibodies against forest cobra toxins

AU - Jensen, Line Ledsgaard

AU - Øhlenschlæger, Mia

AU - Karatt-­Vellatt, Aneesh

AU - Andersen, Mikael Rørdam

AU - Harrison, Robert

AU - Casewell, Nicholas

AU - McCafferty, John

AU - Laustsen, Andreas Hougaard

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N2 - Snakebite envenoming is one of the world’s most neglected diseases and it constitutes a serious global health challenge in tropical regions of the world. Each year, snakebite envenoming has a death toll of 125,000 and causes 400,000 amputations. The only effective therapy is antivenom (purified IgGs from venom-immunized horses/sheep), which is often associated with severe adverse reactions to the i.v. administration of large volumes of equine/ovine IgGs. The forest cobra, N. melanoleuca, is the largest cobra species in Africa and of high medical relevance according to the World Health Organization. N. melanoleuca venom derives its toxicity from potent type I and II α-neurotoxins that target nicotinic acetylcholine receptors, causing inhibition of neuromuscular transmission. This inhibition manifests itself clinically as descending neuromuscular paralysis. Here, we report the most recent results of our ongoing work aiming at identifying human antibodies with neutralizing effects against the medically most important toxins from N. melanoleuca venom. Using phage display selection, we discovered a range of different human scFv antibodies from the IONTAS phage display library. These antibodies are currently undergoing further assessment (binding capacity and cross-reactivity to other toxins) with the aim of converting the most promising candidates into the fully human IgG format for preclinical studies. We hope that this work will help pave the way for the first recombinant snakebite antivenom based on oligoclonal mixtures of human IgG antibodies targeting medically relevant toxins from African elapid snake species.

AB - Snakebite envenoming is one of the world’s most neglected diseases and it constitutes a serious global health challenge in tropical regions of the world. Each year, snakebite envenoming has a death toll of 125,000 and causes 400,000 amputations. The only effective therapy is antivenom (purified IgGs from venom-immunized horses/sheep), which is often associated with severe adverse reactions to the i.v. administration of large volumes of equine/ovine IgGs. The forest cobra, N. melanoleuca, is the largest cobra species in Africa and of high medical relevance according to the World Health Organization. N. melanoleuca venom derives its toxicity from potent type I and II α-neurotoxins that target nicotinic acetylcholine receptors, causing inhibition of neuromuscular transmission. This inhibition manifests itself clinically as descending neuromuscular paralysis. Here, we report the most recent results of our ongoing work aiming at identifying human antibodies with neutralizing effects against the medically most important toxins from N. melanoleuca venom. Using phage display selection, we discovered a range of different human scFv antibodies from the IONTAS phage display library. These antibodies are currently undergoing further assessment (binding capacity and cross-reactivity to other toxins) with the aim of converting the most promising candidates into the fully human IgG format for preclinical studies. We hope that this work will help pave the way for the first recombinant snakebite antivenom based on oligoclonal mixtures of human IgG antibodies targeting medically relevant toxins from African elapid snake species.

U2 - 10.1016/j.toxicon.2018.10.179

DO - 10.1016/j.toxicon.2018.10.179

M3 - Conference abstract in journal

VL - 158

SP - S51-S52

JO - Toxicon

JF - Toxicon

SN - 0041-0101

IS - Suppl. 1

M1 - 170

ER -

Jensen LL, Øhlenschlæger M, Karatt-­Vellatt A, Andersen MR, Harrison R, Casewell N et al. Discovery of human antibodies against forest cobra toxins. Toxicon. 2019;158(Suppl. 1):S51-S52. 170. https://doi.org/10.1016/j.toxicon.2018.10.179