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Stopping Malaria at the Placenta

2 November 2004 (All day)
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Sticky rascal. The VAR2CSA protein (with green-labeled antibodies attached) helps malaria-infected red blood cells latch onto the placenta.

Malaria infects 30 million pregnant women a year, causing anemia and other problems that kill about 200,000 newborns. Now researchers have pinpointed a protein that the parasite needs to infect the placenta--a first step toward a vaccine that could prevent malaria in pregnant women.

Most adults who live where malaria is endemic have developed immunity. The exceptions are women pregnant with their first or second child; a particular strain of parasite infects red blood cells and causes them to accumulate in the woman's placenta, leading to severe malaria, premature births, low-birth-weight infants, and stillbirths.

In 1995, researchers found the first clues that explained why these women were vulnerable. In pregnant women, infected red blood cells stick to chondroitin sulfate A (CSA), a sugary molecule made only by the placenta. To find out how they stick, parasitologist Thor Theander of the University of Copenhagen in Denmark and his colleagues looked for parasite genes that turn on in the presence of CSA. They reported in 2003 that a gene called VAR2CSA, which encodes a protein that the parasite inserts onto the red-blood-cell membrane, revs up when it encounters CSA.

To see if the parasite uses its VAR2CSA protein to make infected red-blood cells stick to the placenta, the researchers made antibodies to VAR2CSA in rabbits, then labeled them with dye. Dye-labeled antibodies to VAR2CSA stuck to spots on the surface of infected red-blood cells that bind to CSA--circumstantial evidence that VAR2CSA was in the right place to get the job done. Dye-labeled antibodies isolated from the blood of infected pregnant women stuck to exactly the same spots, showing that humans, too, could produce antibodies that targeted that protein.

Women with fewer antibodies--and hence a weaker immune response--against VAR2CSA were four times more likely than women with high levels of antibody to give birth to seriously underweight infants, suggesting that they didn't fight off the parasite as well, according to the team's report in the 1 November issue of The Journal of Experimental Medicine. Because the VAR2CSA gene is widely conserved among strains of parasites, the researchers believe a vaccine containing part of the VAR2CSA protein might make an effective vaccine against pregnancy-associated malaria.

"It's definitive, high-quality work that verifies the target for a vaccine" against pregnancy-associated malaria, says molecular parasitologist Kirk Deitsch of Weill Medical College of Cornell University in New York. The strain-specific vaccine strategy might also work to prevent P. falciparum infections of the brain, he says, meaning that "you could eliminate two of the three major causes of death from malaria."

Related sites
Facts on malaria during pregnancy from the Centers for Disease Control and Prevention
More information on pregnancy-associated malaria from the World Health Organization

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