Refining, reducing and replacing in vivo WHO-standard preclinical assays of snake venom pathology and antivenom efficacy

The Alistair Reid Venom Research Unit (ARVRU) of the Liverpool School of Tropical Medicine (LSTM) and MicroPharm Ltd. have a long association in the production and delivery of life-saving snake antivenoms for West Africa, which suffers the continent's highest snakebite mortality burden. Antivenom is the mainstay of snakebite treatment and is immunoglobulin purified from the sera of venom-immunised horses and sheep. There is a legal/regulatory requirement to conduct in vivo preclinical efficacy testing of new and existing antivenoms prior to human treatment. These assays carry a 'substantial' severity grading by the UK Home Office.

The objective of this PhD Studentship is to assess whether a cell-based system can be used to replace in vivo preclinical testing, and to determine the extent to which various 3R-modifications can be incorporated into these assays to reduce the numbers of animals and the associated pain, suffering and distress whilst retaining the scientific/regulatory validity of the assays.

Herrera C et al. (2018). Analgesic effect of morphine and tramadol in standard toxicity assays in mice injected with venom of the snake Bothrops asper. Toxicon 154:35-41. https://doi.org/10.1016/j.toxicon.2018.09.012  

Gutiérrez JM et al. (2017). Snakebite envenoming. Nature Reviews. Disease Primers 3:17079. doi: 10.1038/nrdp.2017.79

Harrison RA et al. (2017). Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. PLoS Negl Trop Dis 11(10). doi: 10.1371/journal.pntd.0005969

Herrera M et al. (2017). Freeze-dried EchiTAb+ICP antivenom formulated with sucrose is more resistant to thermal stress than the liquid formulation stabilized with sorbitol. Toxicon 133:123-126. doi: 10.1016/j.toxicon.2017.05.006

Pla D et al. (2017). What killed Karl Patterson Schmidt? Combined venom gland transcriptomic, venomic and antivenomic analysis of the South African green tree snake (the boomslang), Dispholidus typusBiochimica et biophysica acta 1861(4):814-23. doi: 10.1016/j.bbagen.2017.01.020

Whiteley G et al. (2016). Stabilising the Integrity of Snake Venom mRNA Stored under Tropical Field Conditions Expands Research Horizons.  PLoS Negl Trop Dis 10(6):e0004615. doi: 10.1371/journal.pntd.0004615

Gutiérrez JM et al. (2015). A Call for Incorporating Social Research in the Global Struggle against Snakebite. PLoS Negl Trop Dis 9(9):e0003960. doi: 10.1371/journal.pntd.0003960

Lecht S et al. (2015). Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochurekiBiochimica et biophysica acta 1850(6):1169-79. doi: 10.1016/j.bbagen.2015.02.002

Archer J et al. (2014). VTBuilder: a tool for the assembly of multi isoform transcriptomes. BMC Bioinformatics 15:389. doi: 10.1186/s12859-014-0389-8

Bolton FM et al. (2014). Production and assessment of ovine antisera for the manufacture of a veterinary adder antivenom. Veterinary Record 174(16):406. doi: 10.1136/vr.102286

Bolton F et al. (2014). Snake antivenom trial. Veterinary Record 174(5):126. doi: 10.1136/vr.g1178

Gutiérrez JM et al. (2014). A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming. Bulletin of the World Health Organization 92(7):526-32. doi: 10.2471/BLT.13.132431

 

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PhD Studentship

Status

Closed

Principal investigator

Dr Robert Harrison

Institution

Liverpool School of Tropical Medicine

Co-Investigator

Professor Richard Pleass
Professor John Landon

Grant reference number

NC/K500288/1

Award date

May 2012 - Apr 2016

Grant amount

£93,063