ArticleThe Journal of infectious diseases2016
VAR2CSA Domain-Specific Analysis of Naturally Acquired Functional Antibodies to Plasmodium falciparum Placental Malaria.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review.BMC medicine · 2020Pooled it
- Exploring theFrontiers in immunology · 2025Article
- Identification ofFrontiers in immunology · 2025Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA.Lab animal · 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
- Tackling variants with antibodies.eLife · 2022Article
- Article
- Expression of Large Full-Length PfEMP1 Proteins in HEK293 Cells.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
- mSphere of Influence: Structural Insights into the Molecular Mechanism Underlying Placental Malaria.mSphere · 2021Article
- Article
- Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA.Nature microbiology · 2021Article
- Poor Birth Outcomes in Malaria in Pregnancy: Recent Insights Into Mechanisms and Prevention Approaches.Frontiers in immunology · 2021Review
- Progress and Insights Toward an Effective Placental Malaria Vaccine.Frontiers in immunology · 2021Review
- Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope.Vaccines · 2020Article
- Article
- Functional Antibodies against Placental Malaria Parasites Are Variant Dependent and Differ by Geographic Region.Infection and immunity · 2019Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPlacental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A. The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion.
methodsIn this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies. Antigen-specific immunoglobulin (Ig) G targeting Duffy binding-like (DBL) domains from different alleles were sequentially purified from plasma pooled from multigravid women and then characterized using enzyme-linked immunosorbent assay, flow cytometry, and antiadhesion assays.
resultsDifferent DBL domain-specific IgGs could react to homologous as well as heterologous antigens and parasites, suggesting that conserved epitopes are shared between allelic variants. Homologous blocking of IE binding was observed with ID1-DBL2-ID2a-, DBL4-, and DBL5-specific IgG (range, 42%-75%), whereas partial cross-inhibition activity was observed with purified IgG specific to ID1-DBL2-ID2a and DBL4 antigens. Plasma retained broadly neutralizing activity after complete depletion of these VAR2CSA specificities.
conclusionsBroadly neutralizing antibodies of multigravidae are not depleted on VAR2CSA recombinant antigens, and hence development of VAR2CSA vaccines based on a single construct and variant might induce antibodies with limited broadly neutralizing activity.
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