标题：Understanding How Plasmodium falciparum Binds to the Placenta and Produces Pathology Provides a Rationale for Pregnancy-Associated Malaria Vaccine Development
摘要：
By adulthood repeated exposure to Plasmodium falciparum, the causative agent of the most severe form of
malaria in humans, can induce semi-immunity to clinical infection. During pregnancy, however, there is a striking
recurrence of severe disease, a syndrome described as pregnancy-associated malaria (PAM). This is caused by P.falciparum-infected erythrocytes binding to receptors on the placental endothelium that are expressed uniquely during
pregnancy. This subset of parasites binds by virtue of expressing a cell surface antigen that is the ligand for the
corresponding endothelial receptor, thereby providing a selective pressure for its clonal expansion. The antigen also
triggers a protective antibody-mediated immune response. With subsequent pregnancies and further exposure to these
variant parasites, antibodies develop earlier and women may experience milder infections. Women with PAM exhibit
more severe malaria infections than do non-gravid women, with 2,500-10,000 deaths each year due to haemolytic
anaemia. PAM also has a detrimental effect on the foetus, increasing the risk of low birth weight, which causes 60,000-
200,000 infant deaths annually in sub-Saharan Africa. Current research aims to produce a vaccine to stimulate
development of antibodies which would be protective against infection with wild-type parasites. This is hampered by
significant diversity in variant surface antigens and available vaccine candidates may only protect women living in
malaria-endemic areas. While placental-parasite interactions are not sufficiently understood, incremental progress is being
made towards producing an effective vaccine. This review focuses on the molecular structures involved in binding to
consider the prospects for a vaccine mimicking naturally-acquired immunity to PAM.
