VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI'.
Many efforts aim at solving the serious problems encountered with immunotherapy against scorpion envenoming. The most attractive approach consists in generating single-chain antibody fragments (scFv) as their pharmaco-kinetic properties should match closely those of the scorpion toxins. Although high affinity scFv reagents have been generated in the past, their production level, stability, and toxin neutralizing capacity remain disappointingly poor. In the current study, we identified one Nanobody (Nb), a single-domain antigen-binding fragment of a dromedary Heavy-chain antibody (HCAb) that recognizes specifically the Androctonus australis hector AahI' toxin. This Nb has excellent production, stability and solubility characteristics. With this Nb we further manufactured a tandem linked bivalent construct and assembled a HCAb with improved antigen binding due to avidity effects. All these constructs were shown in mouse models to possess a scorpion toxin neutralization capacity that exceeds by far all previous attempts with scFv-based materials, even when used at lower doses. It is therefore clear that in the near future Nanobodies will be at the core of novel serotherapeutics as they combine multiple benefits over other reagents to treat scorpion envenomed patients.
Hmila
Issam
I
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis, Tunisia.
Abdallah R
Ben Abderrazek-Ben
BA
Saerens
Dirk
D
Benlasfar
Zakaria
Z
Conrath
Katja
K
Ayeb
Mohamed El
ME
Muyldermans
Serge
S
Bouhaouala-Zahar
Balkiss
B
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D002162:Camelus / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D012605:Scorpions
D000906:Antibodies; D011994:Recombinant Proteins; D012604:Scorpion Venoms