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PhD Studentship

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

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At a glance

Completed
Award date
May 2012 - April 2016
Grant amount
£93,063
Principal investigator
Dr Robert Harrison

Co-investigator(s)

Institute
Liverpool School of Tropical Medicine

R

  • Reduction
  • Replacement
Read the abstract
View the grant profile on GtR

Contents

Application abstract

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.

Impacts

Publications

  1. 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  
  2. Gutiérrez JM et al. (2017). Snakebite envenoming. Nature Reviews. Disease Primers 3:17079. doi: 10.1038/nrdp.2017.79
  3. 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
  4. 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
  5. 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 typus. Biochimica et biophysica acta 1861(4):814-23. doi: 10.1016/j.bbagen.2017.01.020
  6. 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
  7. 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
  8. Lecht S et al. (2015). Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki. Biochimica et biophysica acta 1850(6):1169-79. doi: 10.1016/j.bbagen.2015.02.002
  9. 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
  10. 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
  11. Bolton F et al. (2014). Snake antivenom trial. Veterinary Record 174(5):126. doi: 10.1136/vr.g1178
  12. 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