Sequence Heterogeneity of the C-terminal, Cys-rich Region of the Merozoite Surface protein-1 (MSP-1) in Field Samples of Plasmodium Falciparum

Mol Biochem Parasitol. 1995 Jul;73(1-2):103-10. doi: 10.1016/0166-6851(95)00102-7.

Abstract

Recent results with primate plasmodia and rodent models of infection have focused attention on the C-terminal region of the merozoite surface protein-1 (MSP-1) as one of the leading candidates for vaccination against the erythrocytic stages of malaria. However, sequence heterogeneity of this region may compromise its use as a vaccine candidate. While the C-terminal region of MSP-1 from the two prototypic alleles of P. falciparum has been shown to be relatively conserved in laboratory-maintained strains, little data exist on sequence heterogeneity of this region in field isolates from diverse geographic areas. To address this question, DNA encoding the C-terminal, Cys-rich region of P. falciparum MSP-1 from field samples was analyzed by a polymerase chain reaction (PCR)-direct sequencing method. Sequence data were consistent with those obtained from laboratory-maintained strains. In 15 isolates from Africa, Asia and Latin America, only a few nucleotide changes were found leading to amino-acid alterations at four positions out of 102 residues. All the variations corresponded to the predicted amino-acid sequence of the other prototype, suggesting that these changes were possibly due to allelic recombinations. The four changes were E-->Q at position 1644 and TSR-->KNG, or KNG-->TSR at positions 1691, 1700 and 1701. Thus, only three patterns of the C-terminal, Cys-rich region of MSP-1, E-TSR, Q-KNG and Q-TSR, were detected. All the Cys residues were conserved. These results support the potential utility of the C-terminal region of MSP-1 as a vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / genetics
  • Base Sequence
  • Conserved Sequence
  • Cysteine / genetics
  • DNA Primers / genetics
  • DNA, Protozoan / genetics
  • Genetic Variation
  • Merozoite Surface Protein 1
  • Molecular Sequence Data
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Protein Precursors / chemistry
  • Protein Precursors / genetics*
  • Protein Precursors / immunology
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / immunology
  • Protozoan Vaccines / genetics

Substances

  • Antigens, Protozoan
  • DNA Primers
  • DNA, Protozoan
  • Merozoite Surface Protein 1
  • Protein Precursors
  • Protozoan Proteins
  • Protozoan Vaccines
  • Cysteine