Progress on the path to a licensed vaccine against Plasmodium falciparum malaria

Infection with Plasmodium falciparum, the cause of the most severe form of malaria, kills at least one million people each year, mainly children, in addition to significant debilitation in further hundreds of millions. Consequently, this disease has a profound socioeconomic impact in endemic countries and hence it has been a focus of global health initiatives for many years. Increased investment in existing control measures, such as insecticide-impregnated bed nets, has been matched by renewed efforts to develop an efficacious vaccine. Sequencing of the genome of P. falciparum has improved knowledge of the malaria parasite’s complex lifecycle, which, combined with a greater understanding of the human immune response to infection, has spawned several novel candidate vaccines over the last two decades. Most notable among these is RTS,S which has shown much promise during a long development process, recently becoming the first candidate vaccine against human malaria to progress into phase 3 clinical trials. There is optimism, therefore, that in the foreseeable future RTS,S may become the first ever licensed vaccine against a parasitic disease in humans. However, this is tempered by unresolved issues surrounding the lack of understanding of its mechanism of protection and doubt cast over its long-term therapeutic potential. While the future of RTS,S as a commercially available product is not certain, it should contribute to the continuing campaign against malaria, if only as a prelude to a more refined second generation vaccine.