title: Sequence heterogeneity of the C-terminal, Cys-rich region of the merozoite surface protein-1 (MSP-1) in field samples of Plasmodium falciparum.
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.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.forename: C A
authors.initials: CA
authors.lastname: Long
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D001483:Base Sequence; D017124:Conserved Sequence; D003545:Cysteine / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D014644:Genetic Variation; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016052:Protozoan Vaccines / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D017931:DNA Primers; D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D003545:Cysteine