Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines.

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 NF54, clinically isolated 3D7, and Plasmodium falciparum research-grade 7G8 blood-stage malaria parasites were cultured separately in GMP-compliant facilities P. falciparum using screened blood components and then cryopreserved to produce three blood-stage malaria cell P. falciparum 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 anti-malarial drug sensitivity of the cell bank in vitro malaria parasites) to ensure they met the criteria to permit product release according to GMP requirements. Results: The NF54, 3D7 and 7G8 cell banks consisted of >78% ring stage parasites with a ring stage P. falciparum parasitaemia of >1.4%. Parasites were viable following thawing. The cell banks were free from contamination in vitro with bacteria, mycoplasma and a broad panel of viruses. The NF54, 3D7 and 7G8 parasites exhibited P. falciparum differential anti-malarial drug susceptibilities. The NF54 and 3D7 parasites were susceptible to all P. falciparum anti-malaria compounds tested, whereas the 7G8 parasites were resistant/had decreased susceptibility P. falciparum to four compounds. Following testing, all defined release criteria were met and the cell banks were P. falciparum deemed suitable for release. Ethical approval has been obtained for administration to human volunteers. Conclusions: The production of cultured blood-stage malaria cell banks represents a suitable approach P. falciparum 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. [ABSTRACT FROM AUTHOR]