Development and evaluation of a new Plasmodium falciparum 3D7 blood stage malaria cell bank for use in malaria volunteer infection studies

Abstract Background New anti-malarial therapeutics are required to counter the threat of increasing drug resistance. Malaria volunteer infection studies (VIS), particularly induced blood stage malaria (IBSM) model, play a key role in accelerating development. Supply reference 3D7-V2 Plasmodium falciparum cell bank (MCB) is limited. This study aimed develop new MCB, and compare safety infectivity this MCB with existing VIS. A second (3D7-V1) developed 1995 was also evaluated. Methods The expanded vitro using bioreactor produce designated 3D7-MBE-008. 3D7-V1 were then evaluated IBSM where healthy participants intravenously inoculated blood-stage parasites. Participants treated artemether-lumefantrine when parasitaemia or clinical thresholds reached. Safety, parasite growth clearance Results expansion produced 200 vials 3D7-MBE-008 4.3%. compares 0.1% < 0.01% MCB. All four (two per MCB) detectable P. after inoculation approximately 2800 For multiplication rate 48 h (PMR ) non-linear mixed effects modelling 34.6 (95% CI 18.5–64.6), similar parental line; both exceeded 10,000/mL by day 8. Growth slower 11.5 [95% 8.5–15.6]), exceeding 10,000 parasites/mL on days 10 8.5. Rapid followed treatment all participants, half-lives 4.01 4.06 (weighted mean 4.04 3.61–4.57]) hours for 4.11 4.52 4.31 4.16–4.47]) 3D7-V1. total 59 adverse events occurred; most mild severity three being severe study. Conclusion safety, profiles closely resemble that its parent, indicating suitability future studies. Trial Registration: Australian Zealand Clinical Trials registry numbers: P3487 (3D7-V1): ACTRN12619001085167. P3491 (3D7-MBE-008): ACTRN12619001079134