Identification of a conserved region of Plasmodium falciparum MSP3 targeted by biologically active antibodies to improve vaccine design

J Infect Dis. 2004 Sep 1;190(5):1010-8. doi: 10.1086/423208. Epub 2004 Jul 27.

Abstract

Merozoite surface protein 3 (MSP3) is a target of antibody-dependent cellular inhibition (ADCI), a protective mechanism against Plasmodium falciparum malaria. From the C-terminal half of the molecule, 6 overlapping peptides were chosen to characterize human immune responses. Each peptide defined at least 1 non-cross-reactive B cell epitope. Distinct patterns of antibody responses, by level and IgG subclass distribution, were observed in inhabitants of a malaria-endemic area. Antibodies affinity purified toward each peptide differed in their functional capacity to mediate parasite killing in ADCI assays: 3 of 6 overlapping peptides had a major inhibitory effect on parasite growth. This result was confirmed by the passive transfer of anti-MSP3 antibodies in vivo in a P. falciparum mouse model. T helper cell epitopes were identified in each peptide. Antigenicity and functional assays identified a 70-amino acid conserved domain of MSP3 as a target of biologically active antibodies to be included in future vaccine constructs based on MSP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / chemistry*
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Disease Models, Animal
  • Drug Design
  • Epitopes, B-Lymphocyte
  • Humans
  • Immunocompromised Host
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Male
  • Mice
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines
  • Recombinant Proteins / immunology

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Protozoan Proteins
  • Protozoan Vaccines
  • Recombinant Proteins
  • merozoite surface protein 3, Plasmodium