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Novel vaccine targets for malaria

Despite extensive research, malaria remains a serious health concern in tropical countries. Targeting the initial stages of infection may be the answer to a successful anti-malaria vaccine.
Novel vaccine targets for malaria
The malaria-causing Plasmodium parasites infect and multiply within red blood cells, inducing the clinical manifestations of malaria. This stage is preceded by a clinically silent phase of parasite replication in the liver, which constitutes an ideal target for anti-malarial prophylactic approaches such as vaccines. Despite efforts, the development of an efficacious vaccine has proved challenging due to the difficulty in identifying target antigens among the thousands of different parasite-encoded proteins.

Scientists on the EU-funded STACOMAL (Regulation of stage conversion in the malaria parasite: molecular insights for novel vaccine strategies) project wished to investigate the molecular mechanisms that drive parasite stage conversion and to identify potential therapeutic or vaccine targets. Towards this goal, they employed genetic approaches to decipher the role of candidate liver stage factors and elucidate how the parasite remodels its antigenic repertoire during the liver stage. Previous work had led to the identification of SLARP (sporozoite and liver stage asparagine-rich protein) as a master regulator of Plasmodium liver stage development.

Researchers observed that although SLARP-knockout parasites showed a complete developmental arrest in infected hepatocytes, they conferred only limited protection in immunised animals. This suggested that some of the genes under SLARP control might be involved in protective immunity.

From a mechanistic point of view, SLARP exerted its regulatory role through other cis-acting elements and through translational repression. This meant that genes under SLARP control were transcribed but the resultant mRNAs were not translated until the parasite infected the liver.

Collectively, these observations provided a better understanding at the molecular level of the process of parasite differentiation in the liver. Dissecting the process of remodelling of the parasite antigenic profile during stage conversion is a pre-requisite for the rational development of novel therapeutic approaches. As a result, the generation of parasite lines with defined defects in stage conversion can aid in the identification of candidate protective antigens in the future. This will also help us understand the phenomenon of parasite dormancy in the liver, a hallmark of the human parasite.

Related information

Keywords

Vaccine, malaria, Plasmodium, red blood cells, liver, SLARP, protective immunity, translational repression
Record Number: 190711 / Last updated on: 2016-12-14
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