Prospects for pregnancy-associated malaria vaccination predicated on antibody-mediated immunity

By adulthood repeated exposure to Plasmodium falciparum 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 up to 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.