Antibodies Against Placental Malaria Differ by Geographic Region

NIAID Now | June 20, 2019

In areas where malaria is prevalent, pregnant women are at high risk of infection by Plasmodium falciparum (P. falciparum), the most common malaria-causing species in Africa. Malaria infection during pregnancy can result in placental malaria, which is marked by the buildup of P. falciparum-infected red blood cells in the placenta. Placental malaria can cause severe anemia in the mother, low birth weight, and premature birth, and it may be fatal for the mother, fetus, or newborn child.

The risk of malaria infection and associated pregnancy complications is greatest for women in their first pregnancy. Malaria in subsequent pregnancies tends to be less severe because women build up immunity to placenta-binding P. falciparum. Previous studies suggest that this immunity is due to antibodies that target a P. falciparum protein called VAR2CSA, leading to an immune response that protects against infection. Therefore, VAR2CSA is a promising target for a vaccine against placental malaria.

To study antibodies that protect against placental malaria, NIAID researchers and their colleagues collected blood samples from pregnant women in Mali and Tanzania when these women gave birth. The study confirmed previous findings that women who had been pregnant more than once had higher anti-VAR2CSA antibody levels compared with women in their first pregnancies. Furthermore, the antibodies produced by women during their second pregnancies were functionally different; the antibodies bound VAR2CSA proteins from two different strains of P. falciparum and at significantly higher levels than in women during their first pregnancy. In addition, the properties of anti-VAR2CSA antibodies differed between women from Mali and women from Tanzania.

These findings support VAR2CSA as a promising target for a placental malaria vaccine. In addition, the results provide new information on differences in the function of anti-VAR2CSA antibodies between different malaria strains and in different geographic regions. Defining the mechanisms by which these antibodies confer protection against placental malaria is critical for designing future vaccines, as well as interpreting results of early phase clinical trials that are currently underway for VAR2CSA vaccine candidates.

Reference: Doritchamou J et al. Functional antibodies against placental malaria parasites are variant dependent and differ by geographic region. Infection and Immunity. 2019 Jun 20; 87(7). pii: e00865-18.

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