Identification of potent nanobodies to neutralize the most poisonous polypeptide from scorpion venom

Rahma Ben Abderrazek, Issam Hmila, Cécile Vincke, Zakaria Benlasfar, Mireille Pellis, Hafedh Dabbek, Dirk Saerens, Mohamed El Ayeb, Serge Muyldermans, Balkiss Bouhaouala-Zahar

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Scorpion venom, containing highly toxic, small polypeptides that diffuse rapidly within the patient, causes serious medical problems. Nanobodies, single-domain antigen-binding fragments derived from dromedary heavy-chain antibodies, have a size that closely matches that of scorpion toxins. Therefore these nanobodies might be developed into potent immunotherapeutics to treat scorpion envenoming. Multiple nanobodies of subnanomolar affinity to AahII, the most toxic polypeptide within the Androctonus australis hector venom, were isolated from a dromedary immunized with AahII. These nanobodies neutralize the lethal effect of AahII to various extents without clear correlation with the kinetic rate constants kon or koff, or the equilibrium dissociation constant, KD. One particular nanobody, referred to as NbAahII10, which targets a unique epitope on AahII, neutralizes 7 LD50 of this toxin in mice, corresponding to a neutralizing capacity of approx. 37000 LD50 of AahII/mg of nanobody. Such high neutralizing potency has never been reached before by any other monoclonal antibody fragment.

Original languageEnglish
Pages (from-to)263-272
Number of pages10
JournalBiochemical Journal
Volume424
Issue number2
DOIs
Publication statusPublished - 1 Dec 2009
Externally publishedYes

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Keywords

  • Anti-venom
  • Dromedary
  • Recombinant antibody
  • Scorpion toxin
  • Single-domain antibody

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Abderrazek, R. B., Hmila, I., Vincke, C., Benlasfar, Z., Pellis, M., Dabbek, H., Saerens, D., El Ayeb, M., Muyldermans, S., & Bouhaouala-Zahar, B. (2009). Identification of potent nanobodies to neutralize the most poisonous polypeptide from scorpion venom. Biochemical Journal, 424(2), 263-272. https://doi.org/10.1042/BJ20090697