Vaccines against malaria

Abstract

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease.

Keywords: P. falciparum; P. vivax; malaria; vaccine.

Figure 1.

Life cycle of the malaria parasite. (1) Malaria infection begins when an infected female Anopheles mosquito bites a person, injecting Plasmodium parasites in the form of sporozoites, into the bloodstream. (2) The sporozoites pass quickly into the human liver. (3) The sporozoites multiply asexually in the liver cells over the next 7–10 days, causing no symptoms. (4) In an animal model, the parasites, in the form of merozoites, are released from the liver cells in vesicles, journey through the heart, and arrive in the lungs where they settle within lung capillaries. The vesicles eventually disintegrate, freeing the merozoites to enter the blood phase of their development. (5) In the bloodstream, the merozoites invade red blood cells (erythrocytes) and multiply again until the cells burst. Then they invade more erythrocytes. This cycle is repeated, causing fever each time parasites break free and invade blood cells. (6) Some of the infected blood cells leave the cycle of asexual multiplication. Instead of replicating, the merozoites in these cells develop into sexual forms of the parasite, called gametocytes, that circulate in the bloodstream. (7) When a mosquito bites an infected human, it ingests the gametocytes, which develop further into mature sex cells called gametes. (8) The fertilized female gametes develop into actively moving ookinetes that burrow through the mosquito's midgut wall and form oocysts on the exterior surface. (9) Inside the oocyst, thousands of active sporozoites develop. The oocyst eventually bursts, releasing sporozoites into the body cavity that travel to the mosquito's salivary glands. (10) The cycle of human infection begins again when the mosquito bites another person.