Serologic markers of previous malaria exposure and functional antibodies inhibiting parasite growth are associated with parasite kinetics following a Plasmodium falciparum controlled human infection
Abstract
BACKGROUND:
We assessed the impact of exposure to P. falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in two cohorts with different levels of previous malarial exposure.
METHODS:
Nine adult males with high (sero-high) and ten with low (sero-low) previous exposure received 3200 PfSPZ of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR). End points were time to parasitemia, adverse events and immune responses.
RESULTS:
Ten of Ten (100%) volunteers in the sero-low and 7 of 9 (77.8%) in the sero-high group developed parasitemia detected by TBS in the first 28 days (p = 0.125). The median time to parasitemia was significantly shorter in the sero-low group [9 days (7.5-11.0) vs.11.3 days (7.5-18.0), log rank test, p=0.005]. Antibody recognition of sporozoites was significantly higher in the sero-high (median 17.93 AU, IQR 12.95-24) than the sero-low volunteers (median 10.54 AU, IQR 8.36-12.12); p=0.006. Presence of blood-stage antibodies was also significantly higher (p=0.0003) in the sero-high group (median 50.98 AU, IQR 22.46-65.07) than in the sero-low group (median 3.16 AU, IQR 2.43-8.71). Growth inhibitory activity (GIA) was significantly higher in the sero-high (median 21.8%, IQR 8.15-29.65) than in the sero-low (median 8.3%, IQR 5.6-10.23) (p=0.025).
CONCLUSION:
CHMI was safe and well tolerated in this population. Individuals with serological evidence of higher malaria exposure were able to better control infection and had higher parasite growth inhibitory activity.
