RTS,S Vaccination Is Associated With Serologic Evidence of Decreased Exposure to

Abstract

The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with the subsequent blood stage of infection. Antibodies against the vaccine target, the circumsporo-zoite protein, have not shown sufficient correlation with risk of clinical malaria to serve as a surrogate for protec-tion. The mechanism by which a vaccine that targets the asymptomatic sporozoite and liver stages protects against disease caused by blood-stage parasites remains unclear. We hypothesized that vaccination with RTS,S protects from blood-stage disease by reducing the num-ber of parasites emerging from the liver, leading to pro-longed exposure to subclinical levels of blood-stage par-asites that go undetected and untreated, which in tur

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