Development and Pre-Clinical Analysis of a Plasmodium Falciparum Merozoite Surface Protein-1(42) Malaria Vaccine

Mol Biochem Parasitol. 2003 May;128(2):195-204. doi: 10.1016/s0166-6851(03)00077-x.

Abstract

Merozoite Surface Protein-1(42) (MSP-1(42)) is a leading vaccine candidate against erythrocytic malaria parasites. We cloned and expressed Plasmodium falciparum MSP-1(42) (3D7 clone) in Escherichia coli. The antigen was purified to greater than 95% homogeneity by using nickel-, Q- and carboxy-methyl (CM)-substituted resins. The final product, designated Falciparum Merozoite Protein-1 (FMP1), had endotoxin levels significantly lower than FDA standards. It was structurally correct based on binding conformation-dependent mAbs, and was stable. Functional antibodies from rabbits vaccinated with FMP1 in Freund's adjuvant inhibited parasite growth in vitro and also inhibited secondary processing of MSP-1(42). FMP1 formulated with GlaxoSmithKline Biologicals (GSK) adjuvant, AS02A or alum was safe and immunogenic in rhesus (Macaca mulatta) monkeys.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Drug Evaluation, Preclinical
  • Female
  • Macaca mulatta
  • Malaria Vaccines / chemistry
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / prevention & control
  • Male
  • Merozoite Surface Protein 1 / classification
  • Merozoite Surface Protein 1 / immunology*
  • Models, Genetic
  • Molecular Sequence Data
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / immunology*
  • Rabbits
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Merozoite Surface Protein 1
  • Vaccines, Synthetic

Associated data

  • GENBANK/Z35327