Protective immunity to liver-stage malaria

Abstract

Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control. In this review, we discuss immunity to liver-stage malaria. It is hoped that the knowledge gained from animal models of malaria immunity will translate into a more powerful and effective vaccine to reduce this global health problem.

Figure 1

Sporozoites are introduced into the skin following a bite from an infected Anopheles mosquito and within a few hours migrate via the blood to the liver where they infect hepatocytes. During the liver phase of disease, which lasts approximately one week in humans, the sporozoites undergo asexual replication and maturation where sporozoites differentiate into schizonts. Eventually the schizont releasing thousands of merozoites into the blood. Merozoites infect red blood cells and undergo another series of asexual replication every 48 hours but this timing may vary depending on the species of Plasmodium. At this stage, the red blood cell bursts and the cycle begins again thus parasite numbers increase every 2 days. Other merozoites develop into immature gametocytes during the blood stage. If a mosquito bites an infected person the gametocytes can be taken up during the blood meal and mature into sporozoites in the mosquito gut. Thus the mosquito acts as a vector transmitting the disease from one human to another.