VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI'.

TitleVHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI'.
Publication TypeJournal Article
Year of Publication2008
AuthorsHmila, I., B. Abderrazek R, D. Saerens, Z. Benlasfar, K. Conrath, M. El Ayeb, S. Muyldermans, and B. Bouhaouala-Zahar
JournalMol Immunol
Volume45
Issue14
Pagination3847-56
Date Published2008 Aug
ISSN0161-5890
KeywordsAnimals, Antibodies, Camels, Humans, Neutralization Tests, Protein Structure, Tertiary, Recombinant Proteins, Scorpion Venoms, Scorpions
Abstract

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.

DOI10.1016/j.molimm.2008.04.011
Alternate JournalMol. Immunol.
PubMed ID18614235