Functional Conservation of the Malaria Vaccine Antigen MSP-119across Distantly Related Plasmodium Species

Nat Med. 2000 Jan;6(1):91-5. doi: 10.1038/71595.

Abstract

The C-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP-119) is at present a leading malaria vaccine candidate. Antibodies against the epidermal growth factor-like domains of MSP-1 19are associated with immunity to P. falciparum and active immunization with recombinant forms of the molecule protect against malaria challenge in various experimental systems. These findings, with the knowledge that epidermal growth factor-like domains in other molecules have essential binding functions, indicate the importance of this protein in merozoite invasion of red blood cells. Despite extensive molecular epidemiological investigations, only limited sequence polymorphism has been identified in P. falciparum MSP-119 (refs. 9-11). This indicates its sequence is functionally constrained, and is used in support of the use of MSP-119 as a vaccine. Here, we have successfully complemented the function of most of P. falciparum MSP-119 with the corresponding but highly divergent sequence from the rodent parasite P. chabaudi. The results indicate that the role of MSP-119 in red blood cell invasion is conserved across distantly related Plasmodium species and show that the sequence of P. falciparum MSP-119 is not constrained by function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Erythrocytes / parasitology
  • Malaria Vaccines
  • Merozoite Surface Protein 1 / chemistry*
  • Merozoite Surface Protein 1 / genetics*
  • Merozoite Surface Protein 1 / immunology
  • Molecular Sequence Data
  • Plasmodium / genetics*
  • Plasmodium / growth & development
  • Plasmodium / immunology
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / immunology*
  • Pyrimethamine / pharmacology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Malaria Vaccines
  • Merozoite Surface Protein 1
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Pyrimethamine