Abstract
Over the last century, a great deal of effort and resources have been poured into the development of vaccines to protect against malaria, particularly targeting the most widely spread and deadly species of the human-infecting parasites: Plasmodium falciparum. Many of the known proteins the parasite uses to invade human cells have been tested as vaccine candidates. However, precisely because of the importance and immune visibility of these proteins, they tend to be very diverse, and in many cases redundant, which limits their efficacy in vaccine development. With the advent of genomics and constantly improving sequencing technologies, an increasingly clear picture is emerging of the vast genomic diversity of parasites from different geographic areas. This diversity is distributed throughout the genome and includes most of the vaccine candidates tested so far, playing an important role in the low efficacy achieved. Genomics is a powerful tool to search for genes that comply with the most desirable attributes of vaccine targets, allowing us to evaluate function, immunogenicity and also diversity in the worldwide parasite populations. Even predicting how this diversity might evolve and spread in the future becomes possible, and can inform novel vaccine efforts.
Highlights
Preventable and curable, malaria is one of the most severe worldwide public health problems, causing crippling disease leading to approximately half a million deaths every year
The most severe disease is caused by Plasmodium falciparum, and much effort has been devoted over decades of research to the development of a vaccine specific to this species [2]
Not much variation was detected between NF54 and the 3D7 clone derived from it, but thousands of single nucleotide polymorphism (SNP), indels and small structural variations, many of which fall in immunologically important regions, were identified in comparisons with the heterologous strains
Summary
Malaria is one of the most severe worldwide public health problems, causing crippling disease leading to approximately half a million deaths every year. The most severe disease is caused by Plasmodium falciparum, and much effort has been devoted over decades of research to the development of a vaccine specific to this species [2]. All stages of the parasite in the human host have been targeted (Figure 1) with the aim of designing vaccines that prevent infection by directing the immune response to the sporozoites, that avoid clinical symptoms and the spread of disease by using the antigens expressed during the blood cycle, or that stop transmission by targeting gametocytes. Targeting gametoIncythtiessgeonfoemairclyeras,ttahgeecsominpltehteionmoofsthqeuwithoowle oseuqludenacveooifdthienPfelacstmioodniusmpfraelcaidparfurmomgenpoemrseo[n3] to person withohuats arefvfeecatliendgthtehfeudllesveteolof pgemnesn,tpoavf icnlgintihceawl dayisteoasstea.rt deciphering their function in the different stages of the life cycle of the parasite. This knowledge has enhanced the understanding of the disease, In this genoamndicstearrtaed, tphroevcidoinmgpalgeetnioomnicolfanthdsecawpehoofltehespeaqruaseitnecinedoifffetrhenet Prelgaisomnsoodfituhme wfoarllcdip[4a]r. CHMI NCT01441167 CHMI NCT00442377 CHMI NCT02613520 Phase I: NCT01988636 CHMI NCT02132299 CHMI NCT02215707 CHMI NCT02115516 CHMI NCT02098590
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