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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Chondroitin sulfate a-adhering Plasmodium falciparum-infected erythrocytes express functionally important antibody epitopes shared by multiple variants
Journal of Immunology, Volume 185, No. 12, Year 2010
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Description
Acquired protection from Plasmodium falciparum placental malaria, a major cause of maternal, fetal, and infant morbidity, is mediated by IgG specific for the P. falciparum erythrocyte membrane protein 1 variant VAR2CSA. This protein enables adhesion of P. falciparum-infected erythrocytes to chondroitin sulfate A in the intervillous space. Although interclonal variation of the var2csa gene is lower than that among var genes in general, VAR2CSA-specific Abs appear to target mainly polymorphic epitopes. This has raised doubts about the feasibility of VAR2CSA-based vaccines. We used eight human monoclonal IgG Abs from affinity-matured memory B cells of P. falciparum-exposed women to study interclonal variation and functional importance of Ab epitopes among placental and peripheral parasites from East and West Africa. Most placental P. falciparum isolates were labeled by several mAbs, whereas peripheral isolates from children were essentially nonreactive. The mAb reactivity of peripheral isolates from pregnant women indicated that some were placental, whereas others had alternative sequestration foci. Most of the mAbs were comparable in their reactivity with bound infected erythrocytes (IEs) and recombinant VAR2CSA and interfered with IE and/or VAR2CSA binding to chondroitin sulfate A. Pair-wise mAb combinations were more inhibitory than single mAbs, and all of the mAbs together was the most efficient combination. Each mAb could opsonize IEs for phagocytosis, and a combination of the eight mAbs caused phagocytosis similar to that of plasma IgG-opsonized IEs. We conclude that functionally important Ab epitopes are shared by the majority of polymorphic VAR2CSA variants, which supports the feasibility of VAR2CSA-based vaccines against placental malaria. Copyright © 2010 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Barfod, Lea K.
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Dobrilovic, Tina
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Magistrado, Pamela A.
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Denmark, London
National Institute for Medical Research
Khunrae, Pongsak
United Kingdom, Cambridge
University of Cambridge
Viwami, Firmine
Benin
Mixte de Recherche 216
Bruun, Jonas
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Dahlbäck, Madeleine A.
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Bernasconi, Nadia L.
Switzerland, Bellinzona
Institute for Research in Biomedicine
Fried, Michal W.
United States, Seattle
Seattle Biomedical Research Institute
John, Davis
India
Kilimanjaro Christian Medical Centre
Duffy, Patrick Emmet
United States, Seattle
Seattle Biomedical Research Institute
Salanti, Ali
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Lanzavecchia, Antonio
Switzerland, Bellinzona
Institute for Research in Biomedicine
Lim, Chwee Teck
Singapore, Singapore City
National University of Singapore
Tuikue-Ndam, Nicaise
Benin
Mixte de Recherche 216
France, Marseille
Ird Institut de Recherche Pour le Developpement
Higgins, Matthew K.
United Kingdom, Cambridge
University of Cambridge
Hviid, Lars
Denmark, Copenhagen
Københavns Universitet
Denmark, Copenhagen
Rigshospitalet
Statistics
Citations: 62
Authors: 17
Affiliations: 10
Identifiers
Doi:
10.4049/jimmunol.1002390
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Locations
Multi-countries
Participants Gender
Female