Replacement in vivo preclinical models to substantially refine and reduce severe protocols used in snakebite envenoming research

Why did we fund this project?

This award aims to refine antivenom efficacy tests in mice by identifying biomarkers of systemic envenoming.

Globally, snakebite envenoming affects around two million people annually predominantly in rural or disadvantaged communities. It can be fatal. There are challenges in ensuring safe, effective antivenoms are accessible for the diverse range of venoms. The gold standard efficacy test recommended by the WHO is the lethality neutralisation assay where antivenom therapies mixed with fatal doses of snakebite venom are administered intravenously to mice to assess the neutralising capacity of the therapy. Many snake venoms are neurotoxic and the assay can lead to severe suffering in the mice due including paralysis, seizures and haemorrhages. The effects can be rapid making management of the animals and the identification of earlier endpoints difficult. Dr Stuart Ainsworth and colleagues will develop a new model for antivenom assessments by administering the venom via clinically relevant routes such as the limbs, rather than intravenously, preventing venom from being immediately systemic. This should slow down the appearance of the most severe affects allowing Stuart to identify biomarkers, such as coagulation enzyme levels, that are indicative of systemic envenoming and to establish improved humane endpoints.

• Meeting: Improving in vivo snake venom research, 26 January 2023