By Sharon Kingman
BioWorld International Correspondent
LONDON ¿ A vaccine to protect unborn children from the effects of malaria during pregnancy, which include premature birth, miscarriage and low birth weight, could be available within the next 10 years. Researchers in Sweden say they have identified a short protein sequence that could form the basis for a vaccine because it can prevent the malaria parasite from binding to the placenta.
Mats Wahlgren, professor of parasitology at the Karolinska Institute in Stockholm, told BioWorld International: ¿This is an exciting finding because we now understand what causes severe disease in pregnant women with malaria. We have applied for a patent to cover the use of this information in making a vaccine, and are looking for partners to help us develop the project.¿
Wahlgren, together with colleagues in Stockholm and at the Experimental Parasitology Unit in Marseille, France, report their findings in a paper in Science titled ¿Role of Nonimmune IgG bound to PfEMP1 in Placental Malaria.¿
An estimated 130 million to 150 million people become infected with malarial parasites every year, and about 2 million of them die each year. Most people who live in areas where malaria is endemic have gained immunity to the parasite by the time they reach puberty, and no longer experience symptoms when infected.
For girls and women, however, the situation changes when they become pregnant. From the second trimester onward, when the placenta develops, infection with Plasmodium falciparum can cause severe symptoms and may be fatal. Even if the mother survives, the pregnancy may come to a premature end. Should the fetus survive, its birth weight may be low.
Some years ago, Wahlgren and his colleagues observed that red blood cells infected by P. falciparum could bind immunoglobulin molecules to their surfaces. They also knew that, during normal pregnancy, the placenta transports immunoglobulins of the type known as IgG from the maternal blood to that of the fetus. By the end of pregnancy, serum levels of IgG in the child are higher than those in the mother.
Putting two and two together, they began to wonder whether red blood cells infected by P. falciparum, and bound to immunoglobulin molecules, bind to the placenta using the immunoglobulin receptors that are present on this tissue. The experiments they carried out to test this hypothesis are described in the Science paper.
They went to Cameroon in West Africa and identified several pregnant women with malaria. At delivery, after obtaining consent, they took samples of the placentas for study. Experiments showed that infected red blood cells that could bind to the IgG class of immunoglobulins were present in all the placental samples but, in general, were absent from the peripheral blood in these women.
A parasite that could bind IgG was cloned and allowed to reproduce, to provide a population of P. falciparum with this characteristic for further study. Tests showed that these parasites could stick to normal human placental tissue in a pattern very similar to that seen in placental malaria.
¿We found that only those parasites that bound IgG to their surfaces would bind directly to placental tissues. This observation argued that this was the mechanism whereby the placenta becomes enriched with parasites,¿ Wahlgren said. ¿We also found that we could block it with all kinds of reagents that could block this kind of interaction.¿ For example, protein A from Staphylococcus aureus, which binds to IgG, was able to stop the infected cells from binding to placental tissue.
The team went on to identify the molecule responsible for the binding, cloned its genetic sequence and expressed this in Escherichia coli.
¿We found that a section of 70 amino acids on one of the domains of the molecule that P. falciparum expresses in red blood cells to allow these to bind IgG was crucial for binding to take place,¿ Wahlgren said. ¿This polypeptide of 70 amino acids can also hinder binding of the infected cells to the placenta, and we believe therefore that it could form the basis for a good vaccine against maternal malaria.¿
Such a vaccine could be given to girls before they reach adolescence, Wahlgren speculated. In the event of pregnancy, when the placenta develops, immunoglobulin receptors specific for IgG would appear in the body for the first time. Following infection with P. falciparum, infected red blood cells coated with IgG would stick to the placental tissue. In vaccinated individuals, however, the vaccine would block binding of these cells to the placenta.
Wahlgren next plans to study the structure of the IgG-binding molecule to be used for vaccine development.