Developing the next generation of anti-venoms to improve management of cobra poisonings in low and middle incoming countries

We propose a different approach to antivenoms, based on recombinant nanobodies (Nbs), targeting the lethal cobra toxins, to reduce morbidity and mortality. Nbs have a high affinity for selected epitopes, allowing rapid recognition of antigens even if bound to cholinergic receptors, combined with a capacity to dislocate neurotoxin from the receptor. This COBRA-NGaV project brings together research teams with extensive experience in venomics and antivenomics to provide the proof-of-concept (PoC) for cobra toxin-specific Nb candidates as a novel generation of antivenoms and to address the dual obstacle to neutralise cobra toxins: weak immunogenicity and fast diffusion. Preliminary results have been obtained so far: i) strong and specific responses were elicited in dromedaries immunised against the toxic fractions of N. legionis, N. haje and N. oxiana; ii) phage display screenings were adopted to rescue strong Nb binders specific towards relevant N. l., N. h. and N. o. toxins; iii) several clusters of Nb sequences specifically binding cobra toxins have been identified. Herein, Nb selections and combinations for optimal synergic effects and best cross-species performances will be generated. Best-in-class candidates will be tested in a pre-clinical study in mice and sheep according to GMP rules. Cost effectiveness will be established.