A key to pregnancy-associated malaria

A malaria protein that traps infected cells in the placenta may provide a promising new target for a vaccine against pregnancy-associated malaria (PAM). Salanti and colleagues show that the malaria protein VAR2CSA is displayed on malaria-infected cells that bind to the placenta, as they report in the November 1 issue of The Journal of Experimental Medicine. This causes a dangerous infection, which puts both mother and developing child at risk.

Most adults living in malaria-endemic locations have antibodies in their circulation that protect them from repeated infection by blocking the ability of parasite-infected cells to lodge in blood vessels. But during pregnancy, placental cells display a unique molecule called CSA that is not found elsewhere. The parasite takes advantage of this by turning on a protein that can bind to CSA and that has never been seen by antibody-producing cells. The absence of blocking antibodies that bind this protein allows the parasite to slip through a loophole in an otherwise effective immune response and establish an infection. The immune cells eventually detect this new malaria protein and produce protective antibodies, which explains why PAM is mainly a risk during first-time pregnancies.

Although a family of related malaria proteins that confer the ability to bind to the placenta had been identified previously, the role of this protein has remained elusive. Salanti et al now show that another member of this protein family, VAR2CSA, is selectively produced on the surface of infected cells that can bind to the placenta. They find that women, but not men, from endemic areas have circulating antibodies that recognize this protein, and that women with high levels of VAR2CSA-specific antibody give birth to heavier babies than those with low levels. These findings suggest that these antibodies have a protective effect and provide hope that VAR2CSA-specific antibodies raised by vaccination may protect women against PAM. The researchers now hope to define a minor piece of this protein that can be used to induce blocking antibodies in women.