Polyspecific snake antivenom: manufacturing method development and toxicity profiling using an invertebrate model

Mender, Mender 2022. Polyspecific snake antivenom: manufacturing method development and toxicity profiling using an invertebrate model. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Snakebite envenoming (SBE) presents unmet challenges particularly in Sub-Saharan Africa (SSA). Almost all SBE in SSA is due to bites by snakes belonging to the Elapidae and Viperidae families. Antivenom is highly effective in treating SBE. However, there is unprecedented shortage of antivenoms in SSA. This requires a significant increase in production of high quality and cost-effective polyspecific antivenoms against the most clinically relevant snake species within the Elapidae and Viperidae families. A manufacturing process was developed to produce equine-derived whole IgG and F(ab’)2 polyvalent antivenoms against ten snake species belonging to the Bitis, Dendroaspis, Echis and Naja genera. Ion exchange chromatography was used to isolate IgG(T) from the rest of the equine IgG subclasses. The binding capacity of the IgG(T)-enriched and IgG(T)-depleted antivenoms was characterised using immunological assays. Galleria mellonella and Vero cell assays were developed to assess snake venom toxicity and antivenom efficacy. The F(ab’)2 antivenom produced in this study demonstrated excellent stability, physicochemical and immunological properties comparable to the original Fav- AfriqueTM product which was terminated in 2014. The IgG(T) subclass accounts for the majority of equine IgG isotype in hyperimmune horse plasma. However, the IgG(T)-depleted antivenom had a higher binding capacity and better venom toxin recognition pattern compared to the IgG(T)-enriched antivenom. The G. mellonella larval model exhibited a statistically significant difference in toxicity profiles between the viper and elapid snake species. Additionally, the larval model was able to differentiate the antivenom efficacy in protecting toxicity induced by the viper and elapid venoms. This supports the implementation of this model as a strong candidate to reduce or replace the current in vivo preclinical tests for snake venom toxicity and antivenom efficacy. Likewise, a dose-and species-dependent cytotoxicity effect was observed in Vero cells treated with viper and elapid venoms. Thus, the sensitivity of Vero cell cytotoxicity assays supports its inclusion as a quality control assay for antivenom.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	24 March 2023
Last Modified:	05 Jan 2024 08:05
URI:	https://orca.cardiff.ac.uk/id/eprint/157924

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