Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming

Issam Hmila, Bernard Cosyns, Hayfa Tounsi, Bram Roosens, Vicky Caveliers, Rahma Ben Abderrazek, Samir Boubaker, Serge Muyldermans, Mohamed El Ayeb, Balkiss Bouhaouala-Zahar, Tony Lahoutte

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Scorpions represent a significant threat to humans and animals in various countries throughout the world. Recently, we introduced Nanobodies (Nbs) to combat more efficiently scorpion envenoming and demonstrated the performance of NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is far more protective than the classic Fab'2 based therapy and is the most efficient antivenom therapy against scorpion sting in preclinical studies. Now we investigate the biodistribution and pharmacokinetics of 99mTc labeled Nbs by in vivo imaging in rodents and compared these data with those of the Fab'2 product (PAS). The pharmacodynamics of the Nbs was investigated in rats by in vivo echocardiography and it is shown that NbF12-10 prevents effectively the hemodynamic disturbances induced by a lethal dose of venom. Moreover, even a late injection of NbF12-10 restores the heart rate and brings the blood pressure to baseline values. Histology confirms that NbF12-10 prevents lung and heart lesions of treated mice after envenoming. In conjunction, in this preclinical study, we provide proof of concept that NbF12-10 prevents effectively the fatal disturbances induced by Androctonus venom, and that the Nanobody based therapeutic has a potential to substitute the classic Fab'2 based product as immunotherapeutic in scorpion envenoming. Further clinical study using larger cohorts of animals should be considered to confirm the full protecting potential of our NbF12-10.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalToxicology and Applied Pharmacology
Volume264
Issue number2
DOIs
Publication statusPublished - 15 Oct 2012
Externally publishedYes

Fingerprint

Single-Domain Antibodies
Scorpions
Venoms
Animals
Scorpion Stings
Pharmacodynamics
Antivenins
Echocardiography
Histology
Pharmacokinetics
Blood pressure
Hemodynamics
Rats
Rodentia
Therapeutics
Heart Rate
Clinical Studies
Blood Pressure
Imaging techniques
Lung

Keywords

  • Tc-Nanobody
  • Biodistribution
  • Scorpion antivenom
  • SPECT
  • Tissue damage
  • Toxin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Pre-clinical studies of toxin-specific Nanobodies : Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming. / Hmila, Issam; Cosyns, Bernard; Tounsi, Hayfa; Roosens, Bram; Caveliers, Vicky; Abderrazek, Rahma Ben; Boubaker, Samir; Muyldermans, Serge; El Ayeb, Mohamed; Bouhaouala-Zahar, Balkiss; Lahoutte, Tony.

In: Toxicology and Applied Pharmacology, Vol. 264, No. 2, 15.10.2012, p. 222-231.

Research output: Contribution to journalArticle

Hmila, I, Cosyns, B, Tounsi, H, Roosens, B, Caveliers, V, Abderrazek, RB, Boubaker, S, Muyldermans, S, El Ayeb, M, Bouhaouala-Zahar, B & Lahoutte, T 2012, 'Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming', Toxicology and Applied Pharmacology, vol. 264, no. 2, pp. 222-231. https://doi.org/10.1016/j.taap.2012.07.033
Hmila, Issam ; Cosyns, Bernard ; Tounsi, Hayfa ; Roosens, Bram ; Caveliers, Vicky ; Abderrazek, Rahma Ben ; Boubaker, Samir ; Muyldermans, Serge ; El Ayeb, Mohamed ; Bouhaouala-Zahar, Balkiss ; Lahoutte, Tony. / Pre-clinical studies of toxin-specific Nanobodies : Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming. In: Toxicology and Applied Pharmacology. 2012 ; Vol. 264, No. 2. pp. 222-231.
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