Late killing of Plasmodium berghei sporozoites in the liver by an anti-circumsporozoite protein antibody.

Abstract

Plasmodium sporozoites are inoculated into the skin during the bite of an infected mosquito. This motile stage invades cutaneous blood vessels to reach the liver and infect hepatocytes. The circumsporozoite protein (CSP) on the sporozoite surface is an important antigen targeted by protective antibodies (Abs) in immunoprophylaxis or elicited by vaccination. Antibody-mediated protection mainly unfolds during parasite skin migration, but rare and potent protective Abs additionally neutralize sporozoite in the liver. Here, using a rodent malaria model, microscopy and bioluminescence imaging, we show a late-neutralizing effect of 3D11 anti-CSP monoclonal antibody (mAb) in the liver. The need for several hours to eliminate parasites in the liver was associated with an accumulation of 3D11 effects, starting with the inhibition of sporozoite motility, sinusoidal extravasation, cell invasion, and terminating with the parasite killing inside the invaded cell. This late-neutralizing activity could be helpful to identify more potent therapeutic mAbs with stronger activity in the liver.