Protective Antibodies against Placental Malaria and Poor Outcomes during Pregnancy, Benin.

Nicaise Tuikue Ndam,Morten A Nielsen,Firmine Viwami,Achille Massougbodji,Nadine Fievet,Ali Salanti,Philippe Deloron,Adrian J.F Luty,Lise Denoeud-Ndam,Justin Doritchamou

doi:10.3201/eid2105.141626

Abstract

Placental malaria is caused by Plasmodium falciparum-infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation. Antibody-mediated immunity to placental malaria is acquired during successive pregnancies, but the target of VAR2CSA-specific protective antibodies is unclear. We assessed VAR2CSA-specific antibodies in pregnant women and analyzed their relationships with protection against placental infection, preterm birth, and low birthweight. Antibody responses to the N-terminal region of VAR2CSA during early pregnancy were associated with reduced risks for infections and low birthweight. Among women infected during pregnancy, an increase in CSA binding inhibition was associated with reduced risks for placental infection, preterm birth, and low birthweight. These data suggest that antibodies against VAR2CSA N-terminal region mediate immunity to placental malaria and associated outcomes. Our results validate current vaccine development efforts with VAR2CSA N-terminal constructs.

Highlights

Tissue sequestration of Plasmodium falciparum–infected erythrocytes drives malaria-related pathologic changes [1]
Sequestration of infected erythrocytes in the placenta is mediated by VAR2CSA, the P. falciparum erythrocyte membrane protein 1 variant that binds to chondroitin sulfate A (CSA) on the syncytiotrophoblast [11,12]
Acquisition of antibodies against VAR2CSA occurs during pregnancy after exposure to infected erythrocytes sequestering in the placenta

Summary

Introduction

Tissue sequestration of Plasmodium falciparum–infected erythrocytes drives malaria-related pathologic changes [1]. Tissue sequestration is primarily mediated by members of the parasite variant antigen family of P. falciparum erythrocyte membrane protein 1, which is expressed on the membrane of infected erythrocytes. These proteins display extensive antigenic variation, concurrently changing receptor recognition, and tissue tropism of infected erythrocytes [2]. Sequestration of infected erythrocytes in the placenta is mediated by VAR2CSA, the P. falciparum erythrocyte membrane protein 1 variant that binds to chondroitin sulfate A (CSA) on the syncytiotrophoblast [11,12]. Acquisition of antibodies against VAR2CSA occurs during pregnancy after exposure to infected erythrocytes sequestering in the placenta Concentrations of these antibodies and those of antibodies that inhibit binding of infected erythrocytes to CSA [13,14] increase with parity. RESEARCH this substudy, we assessed the effect of antibody response to placental infected erythrocytes, measured early in pregnancy and at delivery, on major pregnancy outcomes

Methods

Results

Conclusion