title: Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines.
abstract: BACKGROUND
  The ability to undertake controlled human malaria infection (CHMI) studies for preliminary evaluation of malaria vaccine candidates and anti-malaria drug efficacy has been limited by the need for access to sporozoite infected mosquitoes, aseptic, purified, cryopreserved sporozoites or blood-stage malaria parasites derived ex vivo from malaria infected individuals. Three different strategies are described for the manufacture of clinical grade cultured malaria cell banks suitable for use in CHMI studies.
  
  
  METHODS
  Good Manufacturing Practices (GMP)-grade Plasmodium falciparum NF54, clinically isolated 3D7, and research-grade P. falciparum 7G8 blood-stage malaria parasites were cultured separately in GMP-compliant facilities using screened blood components and then cryopreserved to produce three P. falciparum blood-stage malaria cell banks. These cell banks were evaluated according to specific criteria (parasitaemia, identity, viability, sterility, presence of endotoxin, presence of mycoplasma or other viral agents and in vitro anti-malarial drug sensitivity of the cell bank malaria parasites) to ensure they met the criteria to permit product release according to GMP requirements.
  
  
  RESULTS
  The P. falciparum NF54, 3D7 and 7G8 cell banks consisted of >78% ring stage parasites with a ring stage parasitaemia of >1.4%. Parasites were viable in vitro following thawing. The cell banks were free from contamination with bacteria, mycoplasma and a broad panel of viruses. The P. falciparum NF54, 3D7 and 7G8 parasites exhibited differential anti-malarial drug susceptibilities. The P. falciparum NF54 and 3D7 parasites were susceptible to all anti-malaria compounds tested, whereas the P. falciparum 7G8 parasites were resistant/had decreased susceptibility to four compounds. Following testing, all defined release criteria were met and the P. falciparum cell banks were deemed suitable for release. Ethical approval has been obtained for administration to human volunteers.
  
  
  CONCLUSIONS
  The production of cultured P. falciparum blood-stage malaria cell banks represents a suitable approach for the generation of material suitable for CHMI studies. A key feature of this culture-based approach is the ability to take research-grade material through to a product suitable for administration in clinical trials.
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. d.stanisic@griffith.edu.au.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. xue.liu@griffith.edu.au.
authors.forename: Xue Q
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. s.de@griffith.edu.au.
authors.forename: Sai Lata
authors.initials: SL
authors.lastname: De
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. m.batzloff@griffith.edu.au.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. t.forbes@griffith.edu.au.
authors.forename: Tanya
authors.initials: T
authors.lastname: Forbes
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. chris.davis@griffith.edu.au.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Davis
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Australia. Silvana.Sekuloski@qimrberghofer.edu.au.
authors.forename: Silvana
authors.initials: S
authors.lastname: Sekuloski
authors.affiliation: Australian Army Malaria Institute, Enoggera, QLD, Australia. Marina.CHAVCHICH@defence.gov.au.
authors.forename: Marina
authors.initials: M
authors.lastname: Chavchich
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Australia. wendychung@celltherapies.com.au.
authors.forename: Wendy
authors.initials: W
authors.lastname: Chung
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Australia. Katharine.Trenholme@qimrberghofer.edu.au.
authors.forename: Katharine
authors.initials: K
authors.lastname: Trenholme
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Australia. James.McCarthy@qimrberghofer.edu.au.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.affiliation: Sanaria Inc, Rockville, MD, USA. tli@sanaria.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Sanaria Inc, Rockville, MD, USA. ksim@sanaria.com.
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.affiliation: Sanaria Inc, Rockville, MD, USA. slhoffman@sanaria.com.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Institute for Glycomics, Griffith University, Southport, QLD, Australia. michael.good@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D018070:Biological Specimen Banks; D002986:Clinical Trials as Topic; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology; D034101:Sporozoites / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology
chemical_list: D000962:Antimalarials; D017780:Malaria Vaccines