Plasmodium falciparum variability and immune evasion proceed from antigenicity of consensus sequences from DBL6ε; generalization to all DBL from VAR2CSA

PLoS One. 2013;8(1):e54882. doi: 10.1371/journal.pone.0054882. Epub 2013 Jan 25.

Abstract

We studied all consensus sequences within the four least 'variable blocks' (VB) present in the DBL6ε domain of VAR2CSA, the protein involved in the adhesion of infected red blood cells by Plasmodium falciparum that causes the Pregnancy-Associated Malaria (PAM). Characterising consensus sequences with respect to recognition of antibodies and percentage of responders among pregnant women living in areas where P. falciparum is endemic allows the identification of the most antigenic sequences within each VB. When combining these consensus sequences among four serotypes from VB1 or VB5, the most often recognized ones are expected to induce pan-reactive antibodies recognizing VAR2CSA from all plasmodial strains. These sequences are of main interest in the design of an immunogenic molecule. Using a similar approach than for DBL6ε, we studied the five other DBL and the CIDRpam from VAR2CSA, and again identified VB segments with highly conserved consensus sequences. In addition, we identified consensus sequences in other var genes expressed by non-PAM parasites. This finding paves the way for vaccine design against other pathologies caused by P. falciparum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Motifs / immunology
  • Amino Acid Sequence
  • Antibodies, Protozoan / blood
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology*
  • Consensus Sequence / immunology
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / immunology
  • Epitopes, B-Lymphocyte / metabolism
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Malaria, Falciparum / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • Plasmodium falciparum / immunology*
  • Pregnancy
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs / immunology*
  • Sequence Alignment
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Immunoglobulin G
  • Peptides
  • VAR2CSA protein, Plasmodium falciparum

Grants and funding

This study received financial support from the Institut de Médecine et d'Epidémiologie Appliquée (grant IMEA-0801), from the European 7th Framework Programme (STOPPAM programme, grant 200889), and from the French National Agency for Research (grant ANR-05-MIME-009-01). C. Badaut was supported by the Institute of Research for Development (IRD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.