New findings could lead to vaccine for severe malaria

The most severe form of malaria hits pregnant women and children the hardest. A joint study between Karolinska Institutet in Sweden and Makerere University in Uganda has now produced some important findings on how the malaria parasite conceals itself in the placenta.

Plasmodium falciparium is the name of by far the most virulent of the four malaria parasites that infect man. It is particularly dangerous in that it also infects the placenta of pregnant women, with fatal consequences for both her and the foetus. This, combined with the often feeble medical resources of malaria-stricken countries, can lead to such serous complications that the mother dies during delivery.

"For some reason, women in their first pregnancy lose the semi-immunity that is normally found in adults," explains Niloofar Rasti, a KI graduate student who has been working with the study. "The placenta seems to be an anatomically favourable environment for a subpopulation of the parasites."

The research group from Karolinska Institutet, under the leadership of Professor Mats Wahlgren, has been working with colleagues from KI's partner university in Uganda to study in detail how the parasite infects the placenta. Their results, which are published in the American scientific journal PNAS, can enable the development of vaccines and therapies to combat severe malarial infections.

During one particular phase of its lifecycle, the parasite enters human red blood cells, where it produces proteins that attach themselves to receptors in the wall of the blood vessels. This causes the red blood cells to accumulate in organ capillaries, and gives rise to life-threatening symptoms. Adults who have been infected several times can become partly immune as their defence system gradually starts to recognise the parasite's proteins. When the placenta is formed, however, a new environment is introduced with a different set of receptors. This means that a new growth niche is made available to a subpopulation of the parasites.

Earlier studies have suggested that each protein from the parasite attaches to only one specific protein, a receptor, in the placenta. Ms Rasti and her colleagues suspected, however, that the natural mechanisms are more complex than laboratory studies have shown. They therefore collected and analysed placentas on site in Uganda.

"Most of the parasites we studied could bind to three different receptors in the placenta," she says. "This would mean that a future vaccine cannot be based on the principle of one protein-one receptor, as was previously believed."

Now that scientists know that several placental receptors are involved in the binding mechanism, attention will be shifted to the parasite itself, and whether it produces many different surface proteins or if one and the same protein is able to bind to many host receptors.

"Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin"

Niloofar Rasti, Fatuma Namusoke, Arnaud Chêne, Qijun Chen, Trine Staalsoe, Mo-Quen Klinkert, Florence Mirembe, Fred Kironde, and Mats Wahlgren

PNAS Online Early Edition, 28 August – 1 September

For further information, please contact:

Professor Mats Wahlgren
The Department of Microbiology, Tumour and Cell Biology (MTC)
Phone: 46-8-524-872-77, 46-70-556-12-46 (mobile)
E-mail: Mats.Wahlgren@ki.se

Graduate Student Niloofar Rasti
The Department of Microbiology, Tumour and Cell Biology (MTC)
Phone: 46-8-457-25-25
E-mail: niloofar.rasti@smi.ki.se

Karolinska Institutet is one of the leading medical universities in Europe. Through research, education and information, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine. For more information, visit ki.se