ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Chondroitin sulfate A-adhering Plasmodium falciparum-infected erythrocytes express functionally important antibody epitopes shared by multiple variants.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The trial behind it
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- High Antibodies to VAR2CSA in Response to Malaria Infection Are Associated With Improved Birthweight in a Longitudinal Study of Pregnant Women.Frontiers in immunology · 2021Trial
- First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites.PLoS pathogens · 2012Trial
- Mechanistic insights into coordinated var transcriptional switching in malaria parasites.The EMBO journal · 2026Article
- VAR2CSA-reactive IgG in Brazilian women exposed toInfection and immunity · 2025Article
- Detection of naturally acquired, strain-transcending antibodies against rosettingInfection and immunity · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Article
- Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA.PLoS pathogens · 2022Article
- Analysis of allelic cross-reactivity of monoclonal IgG antibodies by a multiplexed reverse FluoroSpot assay.eLife · 2022Article
- Production of PfEMP1-Specific Human Monoclonal Antibodies from Naturally Immune Individuals.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Production of PfEMP1-Specific Mouse Monoclonal Antibodies.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Allelic variants of full-length VAR2CSA, the placental malaria vaccine candidate, differ in antigenicity and receptor binding affinity.Communications biology · 2021Article
- Progress and Insights Toward an Effective Placental Malaria Vaccine.Frontiers in immunology · 2021Review
- Article
- Functional Antibodies against Placental Malaria Parasites Are Variant Dependent and Differ by Geographic Region.Infection and immunity · 2019Article
- Immunization with Recombinant Plasmodium falciparum Erythrocyte Membrane Protein 1 CIDRα1 Domains Induces Domain Subtype Inhibitory Antibodies.Infection and immunity · 2018Article
- Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria.Infection and immunity · 2018Article
- Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes.Malaria journal · 2018Article
- Evaluating antibody functional activity and strain-specificity of vaccine candidates for malaria in pregnancy using in vitro phagocytosis assays.Parasites & vectors · 2018Article
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 11 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.