Developing the next generation of anti-venoms to improve management of cobra poisonings in low- and middle-income countries
Prof Balkiss Bouhaouala-Zahar
Institut Pasteur de Tunis, Tunisia
We propose a different approach to antivenoms, based on recombinant nanobodies (Nbs) that target the lethal cobra toxins, to reduce morbidity and mortality. Nbs have a high affinity for selected epitopes that allow rapid recognition of antigens, even if bound to cholinergic receptors, combined with a capacity to dislocate neurotoxins from the receptor.
This COBRA-NGaV project brings together research teams with extensive experience in venomics and antivenomics. It will provide the proof-of-concept for cobra toxin-specific Nb candidates as a novel generation of antivenoms, and address the dual obstacle to neutralise cobra toxins: weak immunogenicity and fast diffusion.
Preliminary results obtained so far:
Strong and specific responses were elicited in dromedaries immunised against the toxic fractions of N. legionis, N. haje and N. oxiana
Phage display screenings were adopted to rescue strong Nb binders specific towards relevant N. l., N. h. and N. o. toxins
Several clusters of Nb sequences specifically binding cobra toxins have been identified.
As a result, we will generate Nb selections and combinations for optimal synergic effects and best cross-species performances. Best-in-class candidates will be tested in a pre-clinical study in mice and sheep according to good manufacturing practice rules.