Novel platforms to develop polyspecifically-effective, safe, affordable and thermostable monoclonal camelid VHH nanobodies to treat snake venom-induced necrosis in India and sub-Saharan Africa
Prof Robert Harrison
Liverpool School of Tropical Medicine, United Kingdom
Each year, 400,000 tropical snakebite victims require life-saving surgical debridement/amputation because there is no medicine to treat the disabling, income-depleting effects of snake venom-induced necrosis. A new therapy is urgently needed to prevent the severe health and socioeconomic consequences for already impoverished victims and health facilities.
Our evidence-underpinned hypothesis is that rationally-selected recombinant, humanised camelid VHH targeting necrosis-inducing venom toxins (NITs) will possess the efficacy, rapid in-tissue distribution, safety, thermostability, affordability and large scale production characteristics appropriate for future development of a community-dispensed therapy. This would be a paradigm shift in the clinical management of venom-induced necrosis to reduce morbidity.
To achieve this for Africa and India, our partners bring new approaches, platforms and required resources to select candidate recombinant NIT-specific monoclonal VHH from (i) B cells of NITimmunised camels and (ii) a synthetic VHH library.
Deploying sequential in vitro, ex vivo human skin and mouse in vivo assays of venom-induced necrosis enables down-selection of the most efficacious, thermostable recombinant VHH. ‘Humanising’ the thermostable recombinant VHH gives us the key safety criterion. E.coli expression enables inexpensive and large-scale production of humanised VHH. These therapy-characteristics and the vast Pan-Africa/India need, provide economy-of-scale production incentives for future manufacturing partners.