Using Cryopreserved Plasmodium falciparum Sporozoites in a Humanized Mouse Model to Study Early Malaria Infection Processes and Test Prophylactic Treatments

Abstract

In addition to vector control, long-lasting insecticidal nets and case management, the prevention of infection through vaccination and/or chemoprevention are playing an increasing role in the drive to eradicate malaria. These preventative approaches represent opportunities for improvement: new drugs may be discovered that target the early infectious stages of the Plasmodium parasite in the liver (rather than the symptomatic, abundant blood stage), and new, exciting vaccination technologies have recently been validated (using mRNA or novel adjuvants). Exploiting these possibilities requires the availability of humanized mouse models that support P. falciparum infection yet avoid the hazardous use of infectious mosquitoes. Here, we show that commercially available P. falciparum sporozoites and FRG mice carrying human hepatocytes and red blood cells faithfully recapitulate the early human malaria disease process, presenting an opportunity to use this model for the evaluation of prophylactic treatments with a novel mode of action.