Poster Presentation First Malaria World Congress 2018

A bioreactor system for the manufacture of genetically modified Plasmodium falciparum blood stage malaria cell banks for in vivo clinical trials (#392)

Rebecca Pawliw 1 , Rebecca Farrow 1 , Silvana Sekuloski 2 , Helen Jennings 1 , Julie Healer 3 , Pri Sathe 3 , Cielo Pasay 1 , Krystal Evans 4 , Alan Cowman 3 , Louis Schofield 5 , James McCarthy 1 , Katharine Trenholme 1
  1. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  2. PharmOut, Brisbane, Queensland, Australia
  3. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  4. BioMelbourne Network, Melbourne, Victoria, Australia
  5. James Cook University, Cairns, QLD, Australia

The use of controlled human malaria infection (CHMI) for testing the efficacy of vaccines and drugs against P. falciparum is now well established. Induced blood stage malaria (IBSM) infection was pioneered at QIMR in the 1990s, and has been subsequently refined. A limiting factor in the IBSM system has been the restricted number of defined P. falciparum strains that are available. A major limitation to date has been obtaining parasitised blood suitable for in vivo studies; until recently it has been necessary to rely on access to deliberately infected volunteers or patients naturally infected with malaria returning from overseas. Both require ethical approval to collect, store and use this material and are subject to concerns about contaminating adventitious infectious agents. Here we describe the successful manufacture of a cell bank of erythrocytes infected with genetically modified P. falciparum parasites using an FDA approved single use, closed system sterile plastic bioreactor system suitable for use in clinical studies. At harvest the cell bank had a parasitaemia of 6.3%, with 96 % of parasites at ring stage. Two hundred vials of the bank were produced with sufficient material available for quality control and ongoing stability testing. This demonstrates that large scale in vitro culture of P. falciparum parasites using a bioreactor can be achieved under GMP compliant conditions, and provides a safe and effective  methodology for the production of malaria parasites suitable for clinical administration. Further, the ability to use infected erythrocytes, including erythrocytes infected with genetically modified parasites, to produce a GMP grade product offers significant opportunities; it opens door for genetically modified parasites to be used as vaccine candidates, and also allows for the number of P .falciparum strains available for IBSM studies to be expanded.