Cited by 98Malaria Research and Controlvaccines and immunoinformatics approachesBlood groups and transfusion

Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P. falciparum placental sequestration

Open access
Dahlbäck, Madeleine, Rask, Thomas S., Andersen, Pernille H., Nielsen, Morten A., Ndam, Nicaise T., Resende, Mafalda, Turner, Louise, Deloron, Philippe +5 more·2006·PLoS Pathogens

Abstract

Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in malaria endemic areas. The syndrome is precipitated by accumulation of infected erythrocytes in placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts and a parasite-encoded protein on the surface of infected erythrocytes, believed to be VAR2CSA. VAR2CSA is a polymorphic protein of approximately 3,000 amino acids forming six Duffy-binding-like (DBL) domains. For vaccine development it is important to define the antigenic targets for protective antibodies and to characterize the consequences of sequence variation. In this study, we used a combination of in silico tools, peptide arrays, and structural modeling to show that sequence variation mainly occurs in regions under strong diversifying selection, predicted to form flexible loops. These regions are the main targets of naturally acquired immunoglobulin gamma and accessible for antibodies reacting with native VAR2CSA on infected erythrocytes. Interestingly, surface reactive anti-VAR2CSA antibodies also target a conserved DBL3X region predicted to form an alpha-helix. Finally, we could identify DBL3X sequence motifs that were more likely to occur in parasites isolated from primi- and multigravidae, respectively. These findings strengthen the vaccine candidacy of VAR2CSA and will be important for choosing epitopes and variants of DBL3X to be included in a vaccine protecting women against pregnancy-associated malaria.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.0020124

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Some sequence motifs on DBL3X were shown to be more likely to occur in parasites isolated from primigravidae than multigravidae.

    “Nevertheless, a similar, but more restricted, process was observed in the expression of VAR2CSA molecules as some sequence motifs on DBL3X were shown to be more likely to occur in parasites isolated from primivs multigravidae (Dahlback et al. , 2006).”

    From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Dahlback et al., 2006

  • Multiple var2csa alleles were found in field isolates.

    “Although var2csa is structurally conserved between P. falciparum isolates and is consistently over-expresssed by placental isolates (Duffy et al. , 2006; Tuikue Ndam et al. , 2005), multiple var2csa alleles were found in field isolates (Dahlback et al. , 2006).”

    From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Dahlback et al., 2006

  • Analysis of var2csa from field isolates has revealed alternating areas of substantial interclonal polymorphism.

    “but analysis of var2csa from field isolates has revealed alternating areas of substantial interclonal polymorphism (Dahlback et al. , 2006; Trimnell et al. , 2006).”

    From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Dahlback et al., 2006

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Dahlbäck, M., Rask, T. S., Andersen, P. H., Nielsen, M. A., Ndam, N. T., Resende, M., Turner, L., Deloron, P., Hviid, L., Lund, O., Pedersen, A. G., Theander, T. G., & Salanti, A.
Affiliations
  • University of Copenhagen (DK)
  • Technical University of Denmark (DK)
  • Institut de Recherche pour le Développement (FR)
Corresponding author
Salanti, Ali
Venue
PLoS Pathogens
Published
2006
Volume
2
Issue
11
Pages
e124
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W2073843808
Cited by
98
References
59
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 6 · 2012: 4
FWCI
11.65
Type
journal article
Language
en
Open access
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Funders
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • National Research Foundation
  • Danmarks Grundforskningsfond
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords
VAR2CSA, Plasmodium falciparum, malaria in pregnancy, placental sequestration, epitope mapping, sequence variation, diversifying selection, antibody accessibility, syncytiotrophoblast, chondroitin sulfate A, vaccine candidate, primigravida, multigravidae, peptide arrays, structural modeling
MeSH terms
Amino Acid Sequence, Animals, Antibodies, Protozoan, Antigens, Protozoan, B-Lymphocytes, Binding, Competitive, Chondroitin Sulfates, Female, Humans, Models, Molecular, Molecular Sequence Data, Parity, Placenta, Plasmodium falciparum, Pregnancy, Receptors, Cell Surface, Recombinant Proteins, Recombination, Genetic, Genetic Variation, Molecular Structure, Protozoan Proteins, Malaria, Falciparum, Protein Structure, Tertiary, Epitope Mapping, Amino Acid Motifs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review