Progressing existing snake venom toxin-specific antibodies into humanised, thermostable monoclonal therapies for preclinical manufacture and clinical trials in Africa and India

Antivenom treatment of snakebite is failing to reduce the annual 138,000 deaths - predominantly in impoverished tropical communities. With a focus upon the most medically-important African and Indian snake venoms, we are developing toxin-neutralising, recombinant, humanised, thermostable monoclonal antibodies (mAbs) that will be more dose- and polyspecifically-effective, affordable and safer than antivenoms, and possess critical economies of scale and manufacturing incentives to secure sustained production/delivery.

We have collected sera and B cells (producing immunoglobulins of distinct structure and therapeutic/mAb-development promise) from:

- multi-envenomed humans

- cows, camels, baboons, mice immunised with the most pathogenic African and Indian venom toxins

- horses used to manufacture African or Indian antivenoms.

Using High-Throughput platforms, we will rank B cells producing these globally-unique animal and human antibodies by in vitro toxin-binding affinity and toxin-function neutralisation, prioritising cross-generic/continental functionality. Genes from top-ranked B cells will be processed into recombinant mAbs (220-500).

Subsequent rounds of in vitro and in vivo (neutralisation of venom-induced lethality in a mouse model of envenoming) down-selection will output 20-40 mAbs for gene-manipulation to deliver 'humanised' and thermostable mAbs.

A final round of in vitro/in vivo selection will deliver 5-10 mAbs/3 mAb mixtures of proven pan-Africa/India polyspecific efficacy for downstream preclinical manufacture and clinical trials.