Complete Attenuation of Plasmodium falciparum Sporozoites by Atovaquone-Proguanil

ABSTRACT: To develop a Plasmodium falciparum (Pf) vaccine that precludes replication inside the host for improved vaccine safety, we tested chemo-attenuation (CVac) of sporozoites (SPZ) with atovaquone-proguanil (AP). In mice, P. berghei sporozoites administered with AP invaded hepatocytes, arrested early, and induced robust protection, which correlated with parasite-specific effector-memory CD8+ T-cell responses. In a clinical trial of PfSPZ-CVac (AP), in which three doses of 5.12x104 or 1.5x105 PfSPZ were administered by direct venous inoculation combined with oral single-dose AP (1,000/400 mg), blood stage infections were fully prevented during immunisation. 2/8 and 2/10 of vaccinees, respectively, were protected when challenged with 3.2x103 PfSPZ 10 weeks later, inferior to PfSPZ-CVac (chloroqui

SUBMITTER: Steffen Borrmann 

PROVIDER: S-SCDT-10_1038-S44321-025-00301-8 | biostudies-other |

REPOSITORIES: biostudies-other