Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria
- Author(s)
- Schofield, L; Hewitt, MC; Evans, K; Siomos, MA; Seeberger, PH;
- Details
- Publication Year 2002-08-15,Volume 418,Issue #6899,Page 785-789
- Journal Title
- NATURE
- Publication Type
- Journal Article
- Abstract
- The malaria parasite Plasmodium falciparum infects 5-10% of the world's population and kills two million people annually(1). 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(2-6); 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 NH2-CH2-CH2-PO4-( Manalpha1-2) 6Manalpha1-2Manalpha1-6Manalpha1-4GlcNH(2)alpha1-6myo-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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- MURINE CEREBRAL MALARIA; TUMOR NECROSIS FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; VASCULAR ENDOTHELIAL-CELLS; PROTEIN-KINASE-C; PLASMODIUM-FALCIPARUM; GLYCOSYLPHOSPHATIDYLINOSITOL TOXIN; SIGNAL-TRANSDUCTION; INTRAERYTHROCYTIC STAGE; MONOCLONAL-ANTIBODY
- Publisher's Version
- https://doi.org/10.1038/nature00937
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-08-15 12:00:00