Vaccines against malaria

Abstract

There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

Figure 1.

Life cycle of the malaria parasite illustrating the various stages that are relevant to vaccine design. These are (1) the anopheline mosquito vector, used in experimental protocols to immunize with irradiated sporozoites administered by mosquito bite; (2) the sporozoite, the target of several vaccines, including RTS,S; (3) the liver-stage, usually targeted by vectored vaccines; (4) the blood-stage, usually targeted by protein in adjuvant vaccine candidates. Merozoite antigens have been most often included in blood-stage vaccines; (5) the gametocyte which along with the ookinete, formed after fertilization in the mosquito midgut, is the source of parasite antigens used in sexual-stage transmission-blocking vaccines. Pre-erythrocytic vaccines, which target the sporozoite and the liver-stage parasite are intended to prevent infection as well as disease while blood-stage vaccines are intended to prevent clinical illness and death.