ArticleCommunications biology2021
Allelic variants of full-length VAR2CSA, the placental malaria vaccine candidate, differ in antigenicity and receptor binding affinity.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Beyond VAR2CSA: redefining the antigenic landscape of placental malaria vaccines.Open research Africa · 2026Review
- Article
- Transcription and Copy Number Variation of Plasmodium falciparum var2csa among Nonpregnant Malaria Patients in Thailand.The American journal of tropical medicine and hygiene · 2025Article
- Antibody levels to variant and conservedFrontiers in immunology · 2025Article
- Exploring theFrontiers in immunology · 2025Article
- Identification ofFrontiers in immunology · 2025Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for a placental malaria vaccine.PLoS pathogens · 2024Article
- Recent Trends in Malaria Vaccine Research Globally: A Bibliometric Analysis From 2005 to 2022.Journal of parasitology research · 2024Review
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.Nature communications · 2023Article
- A conformational epitope in placental malaria vaccine antigen VAR2CSA: What does it teach us?PLoS pathogens · 2023Article
- 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
- Polymorphic Molecular Signatures in Variable Regions of thePathogens (Basel, Switzerland) · 2022Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum-infected erythrocytes (IE) sequester in the placenta via surface protein VAR2CSA, which binds chondroitin sulfate A (CSA) expressed on the syncytiotrophoblast surface, causing placental malaria (PM) and severe adverse outcomes in mothers and their offspring. VAR2CSA belongs to the PfEMP1 variant surface antigen family; PfEMP1 proteins mediate IE adhesion and facilitate parasite immunoevasion through antigenic variation. Here we produced deglycosylated (native-like) and glycosylated versions of seven recombinant full-length VAR2CSA ectodomains and compared them for antigenicity and adhesiveness. All VAR2CSA recombinants bound CSA with nanomolar affinity, and plasma from Malian pregnant women demonstrated antigen-specific reactivity that increased with gravidity and trimester. However, allelic and glycosylation variants differed in their affinity to CSA and their serum reactivities. Deglycosylated proteins (native-like) showed higher CSA affinity than glycosylated proteins for all variants except NF54. Further, the gravidity-related increase in serum VAR2CSA reactivity (correlates with acquisition of protective immunity) was absent with the deglycosylated form of atypical M200101 VAR2CSA with an extended C-terminal region. Our findings indicate significant inter-allelic differences in adhesion and seroreactivity that may contribute to the heterogeneity of clinical presentations, which could have implications for vaccine design.
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