VAR2CSA domains expressed in Escherichia coli induce cross-reactive antibodies to native protein

J Infect Dis. 2008 Apr 15;197(8):1119-23. doi: 10.1086/529526.

Abstract

The variant surface antigen VAR2CSA is a pregnancy malaria vaccine candidate, but its size and polymorphism are obstacles to development. We expressed 3D7-type VAR2CSA domains in Escherichia coli as insoluble His-tagged proteins (Duffy binding-like [DBL] domains DBL1, DBL3, DBL4, and DBL5) that were denatured and refolded or as soluble glutathione S-transferase-tagged protein (DBL6). Anti-DBL5 antiserum cross-reacted with surface proteins of chondroitin sulfate A (CSA)-binding laboratory strains (3D7-CSA and FCR3-CSA) and a clinical pregnancy malaria isolate, whereas anti-DBL6 antiserum reacted only to 3D7 surface protein. This is the first report that E. coli-expressed VAR2CSA domains induce antibody to native VAR2CSA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / biosynthesis
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • DNA, Protozoan / chemistry
  • DNA, Protozoan / genetics
  • Erythrocytes / parasitology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Humans
  • Malaria, Falciparum / parasitology
  • Molecular Sequence Data
  • Phylogeny
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Polymerase Chain Reaction
  • Pregnancy
  • Pregnancy Complications, Parasitic / parasitology
  • Protein Structure, Tertiary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sequence Alignment

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • DNA, Protozoan
  • Recombinant Proteins
  • VAR2CSA protein, Plasmodium falciparum