Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites

Abstract

Controlled human malaria infection with sporozoites is a standardized and powerful tool for evaluation of malaria vaccine and drug efficacy but so far only applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes. We assessed in an open label Phase 1 trial, infection after intradermal injection of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers. Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of 6 volunteers in each group. There were no differences between groups in time until parasitemia by microscopy or quantitative polymerase chain reaction, parasite kinetics, clinical symptoms, or laboratory values. This is the first successful infection by needle and syringe with PfSPZ manufactured in compliance with regulatory standards. After further optimization, the use of such PfSPZ may facilitate and accelerate clinical development of novel malaria drugs and vaccines.

Figure 1.

Parasite density as measured by quantitative polymerase chain reaction (qPCR) in the 2,500 (A), 10,000 (B), and 25,000 (C) PfSPZ Challenge dose groups. Panels A, B, and C show geometric mean parasite density of positive volunteers per group with confidence intervals (N = 5 for all groups) from day of inoculation through last day of positivity after initiation of treatment. Panel D shows an overlay of geometric mean parasite densities of positive volunteers in each group.

Figure 2.

Number of possibly, probably, or definitely related solicited and unsolicited adverse events reported over time in the 2,500 (black dashed), 10,000 (red dotted), and 25,000 PfSPZ Challenge dose (green straight) groups.