Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria

Nature. 2002 Aug 15;418(6899):785-9. doi: 10.1038/nature00937.


The malaria parasite Plasmodium falciparum infects 5-10% of the world's population and kills two million people annually. Fatalities are thought to result in part from pathological reactions initiated by a malarial toxin. Glycosylphosphatidylinositol (GPI) originating from the parasite has the properties predicted of a toxin; however, a requirement for toxins in general and GPI in particular in malarial pathogenesis and fatality remains unproven. As anti-toxic vaccines can be highly effective public health tools, we sought to determine whether anti-GPI vaccination could prevent pathology and fatalities in the Plasmodium berghei/rodent model of severe malaria. The P. falciparum GPI glycan of the sequence NH(2)-CH(2)-CH(2)-PO(4)-(Man alpha 1-2)6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcNH(2)alpha 1-6myo-inositol-1,2-cyclic-phosphate was chemically synthesized, conjugated to carriers, and used to immunize mice. Recipients were substantially protected against malarial acidosis, pulmonary oedema, cerebral syndrome and fatality. Anti-GPI antibodies neutralized pro-inflammatory activity by P. falciparum in vitro. Thus, we show that GPI is a significant pro-inflammatory endotoxin of parasitic origin, and that several disease parameters in malarious mice are toxin-dependent. GPI may contribute to pathogenesis and fatalities in humans. Synthetic GPI is therefore a prototype carbohydrate anti-toxic vaccine against malaria.

Publication types

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

MeSH terms

  • Acidosis / complications
  • Acidosis / prevention & control
  • Animals
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology
  • Antitoxins / immunology*
  • Carbohydrate Sequence
  • Disease Models, Animal
  • Glycosylphosphatidylinositols / chemical synthesis*
  • Glycosylphosphatidylinositols / chemistry
  • Glycosylphosphatidylinositols / immunology*
  • Malaria / complications
  • Malaria / immunology
  • Malaria / prevention & control*
  • Malaria Vaccines / chemical synthesis
  • Malaria Vaccines / chemistry
  • Malaria Vaccines / immunology*
  • Malaria, Cerebral / complications
  • Malaria, Cerebral / immunology
  • Malaria, Cerebral / prevention & control
  • Mice
  • Molecular Sequence Data
  • Plasmodium falciparum / chemistry
  • Plasmodium falciparum / immunology*
  • Plasmodium falciparum / pathogenicity*
  • Pulmonary Edema / complications
  • Pulmonary Edema / prevention & control


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Antitoxins
  • Glycosylphosphatidylinositols
  • Malaria Vaccines