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High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

Authors :
Rose G. F. Leke
Carole A. Long
Kavita Singh
Ali Salanti
Yeung Lo Tutterrow
Diane Wallace Taylor
Joseph D. Smith
Robert J. I. Leke
Marion Avril
Grace Sama
Source :
Infection and Immunity; Vol 80
Publication Year :
2012
Publisher :
AMER SOC MICROBIOLOGY, 2012.

Abstract

Placental malaria, caused by sequestration of Plasmodium falciparum -infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.

Details

Language :
English
ISSN :
00199567
Volume :
80
Issue :
4
Database :
OpenAIRE
Journal :
Infection and Immunity
Accession number :
edsair.doi.dedup.....360421c6999f10caa9914225ec50756a
Full Text :
https://doi.org/10.1128/iai.00071-12